[P] Lec 02.2: Acquired, Adaptive or Specific Immunity Flashcards
(138 cards)
1
Q
- This refers to host response to foreign agents that depends on T and B lymphocytes and is characterized by specificity, memory, and recognition of self versus non-self
- Third line of defense
A
Acquired, Adaptive or Specific Immunity
2
Q
What are the 2 parts of adaptive immune system
A
- Antibody-Mediated Immunity
- Cell-Mediated Immunity
3
Q
Identify what part of adaptive immune system:
- exposure of the body to an antigen can result in the activation of B cells and the production of antibodies
- effective against extracellular antigens, such as bacteria, viruses (when outside cells), and toxins
- Also involved with certain allergic reactions
A
Antibody-Mediated Immunity
4
Q
Identify what part of adaptive immune system:
- Function of cytotoxic T cells and is most effective against microorganisms that live inside the cells (intracellular) of the body (viruses and bacteria)
- It is also involved with some allergic reactions, control of
tumors, and graft rejection
A
Cell-Mediated Immunity
5
Q
Determine if Antibody-Mediated Immunity (Humoral Immunity) or Cell-Mediated Immunity (Cellular Immunity):
- Cell-Mediated
- Acts Against Intracellular Pathogen
- Virus, Fungi, Parasites, Mycobacteria, Tumor Cells
- T Lymphocyte
- Produce Cytokines
- Elimination Of Tumor Cell, Graft Rejection, Hypersensitivity Reaction
A
Cellular Immunity
6
Q
Determine if Antibody-Mediated Immunity or Cell-Mediated Immunity
- Antibody-Mediated
- Acts Against Extracellular Pathogen
- Bacteria
- B Lymphocyte
- Produce Antibody
- Antibody-dependent Cell-mediated Cytolysis (ADCC)
A
Antibody-Mediated Immunity (Humoral Immunity)
7
Q
T or F
Adaptive immunity starts with antigen presentation by Antigen Presenting Cells (Dendritic cells, Monocytes, Macrophages, B cells)
A
T
8
Q
What are the 2 types of Responses of Adaptive Immunity
A
- Humoral
- Cellular
9
Q
2 types of Responses of Adaptive
Immunity:
- Non-cellular elements in the blood were responsible for protection from
microorganisms
A
Humoral
10
Q
2 types of Responses of Adaptive Immunity: Humoral
2 types of immunity under humoral
A
- Active
- Passive
11
Q
2 types of immunity under humoral
- Action is involved
- The body forms the antibodies. The person produces his own antibodies
- Has two types: Natural, Artificial
A
Active Immunity
12
Q
2 types of immunity under humoral: Active immunity
- The host is exposed to foreign immunogen as a result of infection and the host’s immune cells manufacture specific products to eliminate foreign immunogen
- convalescent immunity that occurs when a person recovers from an infection
Its types
A
Natural Active
13
Q
2 types of immunity under humoral: Active immunity
- Immune system responds to an altered organism/non-infectious organism
- Immunity acquired by injection of synthetic or biological preparations such as vaccine, toxin, and toxoid
Its types
A
Artificial Active
14
Q
2 types of immunity under humoral
- No action involved
- The body or person merely received antibodies
- Also has 2 types: Natural, Artificial
A
Passive
15
Q
2 types of immunity under humoral: Passive
- Crosses placenta to protect infant
- Immunity resulting from the utero transfer to the fetus of antibodies formed earlier in the mother protects the newborn child during the first months of life against some common infections
Its types
A
Natural Passive
16
Q
2 types of immunity under humoral: Passive
- Immune product from another animal injected into the host
- Immunity acquired by injection of immune sera or antitoxin originally manufactured by an animal (ex: horse)
A
Artificial Passive
17
Q
2 types of immunity under humoral
Identify what type of humoral response and also what specific type
Mode of Acquisition: Infection
Antibody Produced by Host: Yes
Immediate Response: No
Duration of Immune Response: Long
A
Natural Active
18
Q
2 types of immunity under humoral
Identify what type of humoral response and also what specific type
Mode of Acquisition: Vaccination
Antibody Produced by Host: Yes
Immediate Response: No
Duration of Immune Response: Long
A
Artificial Active
19
Q
2 types of immunity under humoral
Identify what type of humoral response and also what specific type
Mode of Acquisition: Transfer In Vitro
or Colostrum
Antibody Produced by Host: No
Immediate Response: Yes
Duration of Immune Response: Short
A
Natural Passive
20
Q
2 types of immunity under humoral
Identify what type of humoral response and also what specific type
Mode of Acquisition: nfusion of Serum
of Plasma Injection
Antibody Produced by Host: No
Immediate Response: Yes
Duration of Immune Response: Short
A
Artificial Passive
21
Q
Active or Passive Immunity?
Participation of “Defense force” of the host: Participates in strictest sense
Relative effectiveness in adult: High
Relative efffectiveness in newborn: Low
Sources of the factors responsible for immunity: No
Way of Production: Natural, Artificial
Immunity Duration: Long
Conferring of Immunity: Latent Period
Negative Phase in Immunity: Present
Reactivation: Easy
A
Active Immunity
22
Q
Active or Passive Immunity?
Participation of “Defense force” of the host: Does not participate in strictest sense
Relative effectiveness in adult: Moderate to low
Relative efffectiveness in newborn: Moderate to high
Sources of the factors responsible for immunity: May inherit from mother
Way of Production: Natural, Artificial
Immunity Duration: Short lived (10-14 days)
Conferring of Immunity: Immediate
Negative Phase in Immunity: Absent
Reactivation: Dangerous
A
Passive
23
Q
2 types of Responses of Adaptive Immunity:
- Cellular elements in the blood were responsible for protection from microorganisms
A
Cell-mediated
24
Q
Two categories of cell-mediated response based on size
A
- Small lymphocytes
- LGL/ Large Granular Lymphocytes
25
Two categories of cell-mediated response based on **size**
* 8-10um
* high nuclear to cytoplasm (N/C) ratio
* lack cytoplasmic granules
Small lymphocytes
26
Two categories of cell-mediated response based on **size**
* diameter of up to 16 um
* smaller N/C ratio than small lymphocytes
* Cytoplasmic granules.
LGL/ Large Granular Lymphocytes
27
What are the cells of adaptive immune system?
T-cell, B-cell
28
# Cells of adaptive immune system
* produce cytokines that contribute to immunity by stimulating B cells to produce antibodies
* assisting in killing tumor cells or infected target cells, and helping to regulate both the innate and adaptive immune
T-cell
29
# Cells of adaptive immune system
2 examples of T-cell?
CD4+, CD8+ cells
30
# Cells of adaptive immune system
What is the normal ratio of CD4+ : CD8+ cell
2:1
| CD4 has to be more numerous
31
# Cells of adaptive immune system
T or F
ratio of CD4+ : CD8+ cell in HIV is 1: 0.5
F (reverse; should be 0.5:1)
| CD4+ decreases since HIV attacks these cells
32
# Cells of adaptive immune system: T-CELL
2 immunologic functions of T-cell:
* cytolysis of virally infected cells & tumor targets
* production
of lymphokine
Effector functions
33
# Cells of adaptive immune system: T-CELL
2 immunologic functions of T-cell:
* ability to amplify or suppress other effector lymphocytes (including T and B cells)
Regulatory functions
34
* a surface marker that identifies a particular cell line or stage of cellular differentiation with a defined structure
* can be identified with a group or cluster of monoclonal antibodies
Cluster of Differentiation
35
# T-CELLS CD MARKERS
**Identify cd marker based on description:**
* sheep red blood cell receptor/ classical T-cell surface marker
* rosette formation with sheep RBC
CD2
36
# T-CELLS CD MARKERS
**Identify cd marker based on description:**
* part of T-cell antigen-receptor complex
* binds to antigen presented by APCs
CD3
37
# T-CELLS CD MARKERS
**Identify cd marker based on description:**
* Receptor for MHC Class II molecule
CD4
38
# T-CELLS CD MARKERS
**Identify cd marker based on description:**
* receptor for MHC Class I molecule
CD8
39
# T-CELLS CD MARKERS
* This molecule found on surface of APC, presents presents extracellular antigens recognized by Tcells using T cell antigen receptor (TCR & CD3)
MHC Class II
40
# SURFACE MARKERS ON T, B, AND NK CELLS
**Identify antigen based on cell type and function:**
Cell type: Thymocytes, T-cells
Function: Found on all T cells;
associated with T-cell antigen receptor
CD3
41
**Identify antigen based on cell type and function:**
Cell type: T helper cells, Monocytes, Macrophages
Function: Identifies T helper cells (also found on most T regulatory cells)
CD4
42
**Identify antigen based on cell type and function:**
Cell type: Thymocyte subsets
Cytotoxic T cells
Function: Identifies cytotoxic T cells (Tc cells)
CD 8
43
**Identify antigen based on cell type and function:**
Cell type: Macrophages, NK cells, Neutrophils
Function: Low-affinity Fc receptor for antibody, mediates phagocytosis
CD 16
| mga 16 mga pHAGO at mahilig kumain NG?/??!
44
**Identify antigen based on cell type and function:**
Cell type: B cells, Follicular dendritic
cells
Function: Part of B-cell coreceptor;
regulates B-cell development and
activation
CD 19
45
**Identify antigen based on cell type and function:**
Cell type: B cells, Follicular dendritic
cells
Function: Receptor for complement component C3d, part of B-cell coreceptor with CD19
CD 21
46
**Identify antigen based on cell type and function:**
Cell type: NK cells, Subsets of T cells
Function: Cell adhesion
CD 56
47
# T-CELL DIFFERENTIATION
1. T-cell Precursors leave the bone marrow and migrate to ?
| what organ
Thymus
48
# T-CELL DIFFERENTIATION
2.Early surface markers on thymocytes that are committed to becoming T-cells include what 2 CD markers?
CD 44, CD 25
49
# Thymocyte Migration
1. Newly arriving thymocytes enter at the (blank)
2. Migrate toward the thymic cortex under direction of (blank)
3. Move from cortex to medulla over a (blank) period
| sensya na di nagrregister blank
1. Cortico-medullary junction
2. Chemokines
3. 3-week
50
# T-CELL DIFFERENTIATION
* This cells are critical for t-cell differentiation
* Include: macrophage, dendritic cells, fibroblasts, thymic epithelial cells
* Maturation period: 3-week period
Thymic stromal cells
51
# T-CELL DIFFERENTIATION
* This is where early precursor T cells (immature T cells) begin their development
Thymus CORTEX
52
# T-CELL DIFFERENTIATION
* This is where mature T cells reside after surviving negative selection
| from chat gpt
## Footnote
negative selection: eliminates self-reactive T cells to prevent autoimmunity
Thymus Medulla
53
Familiarize the ontogeny of lymphoid cells
## Footnote
ontogeny - step-by-step maturation of lymphoid cells,
1. T Cell Differentiation (T cells develop from stem cells and mature in the thymus)
2. Double-Negative Thymocyte (Immature T cells lack CD4 and CD8 markers at this stage)
3. Double-Positive Thymocytes (T cells express both CD4 and CD8 before undergoing selection)
4. Single Positive (T cells commit to either CD4 (helper) or CD8 (cytotoxic) roles)
5. Mature T Cell ( Fully developed T cells enter circulation but remain naïve)
6. Activated T Cell (T cells recognize an antigen and trigger an immune response)
7. Sensitized T Cell (Memory T cells remember past infections for faster future responses.)
| chat gpt based explanation for clarification only!
54
# ONTOGENY OF LYMPHOID CELLS
* Thymocytes undergo V(D)J recombination, which is a process that involves the random rearrangement of TCR gene segments to create a
unique TCR
* *Happens in the Double-Negative Thymocyte stage*.
a. REARRANGEMENT
OF T CELL
RECEPTOR
b. CHANGES IN
EXPRESSION OF
THYMOCYTE CELL
SURFACE MARKERS
c. SELECTION OF
THYMOCYTES WITH
FUNCTIONAL
RECEPTORS
d. DELETION OF
THYMOCYTES WITH
SELF-REACTIVE
POTENTIA
| SELECT SPECIFIC PROCESS
REARRANGEMENT
OF T CELL
RECEPTOR
55
# ONTOGENY OF LYMPHOID CELLS
* Thymocytes express different cell surface markers at different stages of their development
* These markers help to identify the stage of development and the type of T cell
* *Occurs when T cells transition from Double-Negative to Double-Positive stages (T-cells expressing expressing CD4 and CD8)*
a. REARRANGEMENT
OF T CELL
RECEPTOR
b. CHANGES IN
EXPRESSION OF
THYMOCYTE CELL
SURFACE MARKERS
c. SELECTION OF
THYMOCYTES WITH
FUNCTIONAL
RECEPTORS
d. DELETION OF
THYMOCYTES WITH
SELF-REACTIVE
POTENTIA
| SELECT SPECIFIC PROCESS
CHANGES IN
EXPRESSION OF
THYMOCYTE CELL
SURFACE MARKERS
56
# ONTOGENY OF LYMPHOID CELLS
* Thymocytes that express functional TCRs are selected to survive and mature, while those that do not express functional TCRs undergo
apoptosis
* Double-Positive stage ( *T cells that successfully bind self-MHC molecules survive, while non-functional ones undergo apoptosis*)
a. REARRANGEMENT
OF T CELL
RECEPTOR
b. CHANGES IN
EXPRESSION OF
THYMOCYTE CELL
SURFACE MARKERS
c. SELECTION OF
THYMOCYTES WITH
FUNCTIONAL
RECEPTORS
d. DELETION OF
THYMOCYTES WITH
SELF-REACTIVE
POTENTIA
| SELECT SPECIFIC PROCESS
SELECTION OF
THYMOCYTES WITH
FUNCTIONAL
RECEPTORS
57
# ONTOGENY OF LYMPHOID CELLS
* Thymocytes that express TCRs that recognize self-antigens are deleted to prevent autoimmune
disease
* *T cells transition to Single-Positive and Mature T Cell stages (T cells that recognize self-antigens too strongly are deleted to prevent autoimmunity)*
a. REARRANGEMENT
OF T CELL
RECEPTOR
b. CHANGES IN
EXPRESSION OF
THYMOCYTE CELL
SURFACE MARKERS
c. SELECTION OF
THYMOCYTES WITH
FUNCTIONAL
RECEPTORS
d. DELETION OF
THYMOCYTES WITH
SELF-REACTIVE
POTENTIA
d. DELETION OF
THYMOCYTES WITH
SELF-REACTIVE
POTENTIAL
58
# DIFFERENT TYPES OF T CELLS
T helper, T cytotoxic, or T regulatory cell?
* CD4+
* Binds to MHC class II
* Release cytokines
* Types: Th 1, Th 2, Th 17, Tfh
T helper
59
T helper, T cytotoxic, or T regulatory cell?
* CD8+
* Kills tumor cells and virally infected cells by binding to MHC class 1
* MHC restricted and antigen specific
* Kills through release of cytotoxic granules (perforins, granzymes)
T cytotoxic
60
# T cytotoxic cells: granules
2 cytotoxic granules present in T cytotoxic cells
* Perforins
* Granzymes
these are also present in NK cells
61
# T cytotoxic cells: granules
* Create pores in target cell membrane, allowing granzymes to enter
Perforins
| POREforins hehe
62
# T cytotoxic cells: granules
* Proteolytic enzymes
* induce apoptosis (programmed cell death) in target cells
Granzymes
63
# DIFFERENT TYPES OF T CELLS
T helper, T cytotoxic, or T regulatory cell?
* CD4+ and CD25+
* CD25 acts as receptor for IL-2-
* Differentiation is stimulated by TGF-β (induces expression of FOXP3 protein)-
* Suppress immune response and prevents autoimmunity
T regulatory cell
64
# DIFFERENT TYPES OF T CELLS: T regulatory cell
CD25 acts as receptor for?
a. IL-1
b. IL-2
c. both
d. neither
b. IL-2
65
# DIFFERENT TYPES OF T CELLS: T regulatory cell
Differentiation is stimulated by ?, which induces expression of FOXP3 protein
a. IL-2
b. PDGF
c. both
d. neither
d. neither
## Footnote
STIMULATED BY TGF-β
66
# DIFFERENT TYPES OF T CELLS: T regulatory cell
T or F
IN T-regulatory cells incolving CD4+ and CD25+, Differentiation is
stimulated by TGF-β which inhibits expression of FOXP3 protein
F (TGF-β **induces** expression of FOXP3 protein)
67
What are the 3 mature T cells mentioned?
CD4+ cells, CD8+ cells, T regulatory cells
68
# 3 Mature T cells
* Recognize antigen along with MHC class II protein
* Also termed as Helper or Inducer Cells
* Commander, appropriate command strategy
* Chooses appropriate immune response depending on the type of pathogen
CD4+ T CELLS
69
# 3 Mature T cells
For CD4+ T-cells, immune response strategy could either be?
a. Intracellular
b. Extracellular
c. both
d. neither
c. both
70
# 3 Mature T cells
* Cell-mediated = Th1 (IFN-y, IL-2, TNF-a)
| Immune response strategy of T-cells
Intracellular
71
# 3 Mature T cells
* Th2 (for B cell activation into plasma cell, antibody production; IL-4,5,6,9,10,13)
* Th17 - IL-17, 22
| Immune response strategy of T-cells
Extracellular
72
# 3 Mature T cells
T or F
Approximately 2/3 of peripheral T cells express CD4 antigen (Th1, Th 2)
T
73
# 3 Mature T cells
**Identify subset of Th cell based on description:**
* secretes **IFN-γ, IL-2 and TNF-a**;
* effective against intracellular pathogens
| y 2 a
Th 1
74
# 3 Mature T cells
**Identify subset of Th cell based on description:**
* secretes **IL-17 and 22**;
* recruits **granulocytes against extracellular bacteria**l infection
Th 17
75
**Identify subset of Th cell based on description:**
* secretes **IL 4,5,6,9,10,13**
* Extracellular parasites and allergens
Th 2
76
**Identify subset of Th cell based on description:**
* remains in the lymph nodes and interacts with B cells and plasma cells there
* provide essential **signaling to B cells** as they undergo processes such as activation, immunoglobulin class switching, affinity maturation, and the formation of B-cell memory.
Tfh (T follicular
helper)
77
# 3 Mature T cells
* Interact with antigen and MHC class I proteins
* Remaining one-third express CD8 antigen
CD8+ T CELLS
78
# 3 Mature T cells
* Possess the CD4 antigen and CD25
* These cells comprise approximately
* 5 to 10 percent of all CD4-positive T cells
* T regs play an important role in suppressing the immune response to self-antigens (suppress or amplify response)
T REGULATORY CELLS (T reg)
79
# CELLS OF THE ADAPTIVE IMMUNE SYSTEM
* Make up approximately 5-15% of circulating lymphocytes
* Classically identified by their cell **surface immunoglobulin**
* Life span- 3-5 days
* Originally found to mature in birds in an organ called “bursa of fabricus” which is similar to appendix of humans
* **Surface immunoglobulin** - traditional marker
* **CD19,20,21**- newest marker
* Activated to **become plasma cell (antibody-producing cell)**
B cells
80
B cells are originally found to mature in birds in an organ called what, which is similar to appendix of humans?
bursa of fabricus
81
Traditional marker of B cells?
Surface immunoglobulin
82
3 newest marker for B cells?
CD 19, 20, 21
83
T or F
Immature B cell are located in the Bone Marrow
T
84
T or F
B cell can be activated by T cytotoxic cell
F (can be activated by T-helper cell)
85
What are the 2 methods of B-cell activation?
* T-dependent antigen
* T-independent
86
# 2 methods of B-cell activation
* Requires T cell in activation
* If T cell is involved: IgM to IgG (Ab isotype can be changed or switched, i.e., classswitching)
* T cells **release cytokines** (end product of T cell activation), which dictate the type of Ab produced by the B cell
T-Dependent Antigens
87
# 2 methods of B-cell activation
T or F
default antibody is IgM
T
88
# 2 methods of B-cell activation
T or F
B cells activated by T helper cell respond better in allergens due to its ability to class switch from antibody IgG to IgE
F (B cells activated by T helper cell respond better in allergens due to its ability to class switch antibody from **IgM to IgE**)
| remember: IgM is default antibading
89
# 2 methods of B-cell activation
* No class switching
* Antibody remains the same, always IgM (macroglobulin, pentamer)
* Identified Via **surface immunoglobulin**
T-Independent
90
T or F
No T cell = no one will dictate the type of
Ab produced
T
91
Familiarize the ONTOGENY OF LYMPHOID CELLS (B CELL DIFFERENTIATION)
1. B cells originate from hematopoietic stem cells in the bone marrow
2. Stem cells give rise to early lymphocyte progenitors, which then develop into B-cell precursors
3. Antigen-independent phase
4. Antigen-dependent phase:
92
# ONTOGENY OF LYMPHOID CELLS (B CELL DIFFERENTIATION)
T or F
B cells orginate from hematopoeitic stem cells in BM
T
93
# ONTOGENY OF LYMPHOID CELLS (B CELL DIFFERENTIATION)
* Formation of distinct subpopulations
* Pro-B cells (progenitor B cells), Pre-B cells (precursor B cells), Immature B cells, Mature B cells
* *This happens in the bone marrow before the B cell encounters any foreign antigen*
Antigen-independent phase
94
# ONTOGENY OF LYMPHOID CELLS (B CELL DIFFERENTIATION)
* Generation of plasma cells and memory B cells after encountering specific antigen
* *Occurs after B cells leave the bone marrow and enter lymphoid organs*
Antigen-dependent phase
95
# STAGES OF B-CELL DEVELOPMENT
**Identify what stage based on key CD markers, B-cell receptor, and MHC**
Key CD markers: CD 10
CD 19
B-cell receptor: ----
MHC: +
Pro-B cell
96
**Identify what stage based on key cd markers, b-cell receptor, and MHC**
Key CD markers: CD 10, 19, **20**
B-cell receptor: Immunoglobulin
(Ig) heavy chain, Surrogate light chain
MHC: +
Pre-B cell
97
**Identify what stage based on key cd markers, b-cell receptor, and MHC**
Key CD markers: CD 10, 19, 20, **21, 40**
B-cell receptor: Immunoglobulin
M (IgM) heavy chains and κ or λ light chains
MHC: ++
Immature B cell
98
**Identify what stage based on key cd markers, b-cell receptor, and MHC**
Key CD markers: CD 19, 20, 21, 40
B-cell receptor: Immunoglobulin
D (IgD) or IgM heavy chains
and κ or λ light chains
MHC: ++
Mature B cell
99
**Identify what stage based on key cd markers, b-cell receptor, and MHC**
Key CD markers: **CD 138**
B-cell receptor: ----
MHC: -
Plasma Cell
100
# Antigen-independent phase: PROgenitor-B CELL
* B-cell progenitors receive signals from bone marrow stromal cells through
cell-to-cell contact and soluble
cytokines (e.g., IL-7)
* Signaling induces expression of transcription factors (e.g., E2A, EBF, IFR8, PAX5)
a. SIGNALING
b. TRANSCRIPTION FACTORS
c. BCR GENE REARRANGEMENT
d. BCR STRUCTURE
e. GENE REARRANGEMENT
PROCESS
f. ALLELIC EXCLUSION
g. PROGRESSION TO NEXT STAGE
| SELECT WHICH SPECIFIC PROCESS
a. SIGNALING
101
# Antigen-independent phase: PROgenitor-B CELL
B-cell progenitors receive signals from
bone marrow stromal cells through?
a. cell to cell contact
b. insoluble cytokine (IL-7)
c. both
d. neither
| 1. SIGNALING
a. cell to cell contact
| 1. Signaling
## Footnote
**b should be soluble cytokine** to be correct
102
# Antigen-independent phase: PROgenitor-B CELL
T or F
Signaling induces expression of
transcription factors (e.g., E2A, EBF,
IFR8, PAX5)
| 1. Signaling
T
103
# Antigen-independent phase: PROgenitor-B CELL
* Control gene expression and drive pro-B cell development
* required for continued survival and development of pro-B cells
a. SIGNALING
b. TRANSCRIPTION FACTORS
c. BCR GENE REARRANGEMENT
d. BCR STRUCTURE
e. GENE REARRANGEMENT
PROCESS
f. ALLELIC EXCLUSION
g. PROGRESSION TO NEXT STAGE
| SELECT SPECIFIC PROCESS
b. TRANSCRIPTION FACTORS
104
# Antigen-independent phase: PROgenitor-B CELL
* Pro-B cells undergo rearrangement of B-cell receptor (BCR) genes
* Rearrangement occurs in a stepwise
manner, beginning with heavy-chain
genes
* BCR is a cell surface version of an
immunoglobulin (antibody molecule)
a. SIGNALING
b. TRANSCRIPTION FACTORS
c. BCR GENE REARRANGEMENT
d. BCR STRUCTURE
e. GENE REARRANGEMENT
PROCESS
f. ALLELIC EXCLUSION
g. PROGRESSION TO NEXT STAGE
BCR GENE REARRANGEMENT
105
# Antigen-independent phase: PROgenitor-B CELL
is a cell surface version of an
immunoglobulin (antibody molecule)
B cell Receptor or BCR
106
# Antigen-independent phase: PROgenitor-B CELL
* Composed of two chains (heavy and light
* Variable regions determine epitope specificity
* Constant regions allow for intracellular signaling and activation
a. SIGNALING
b. TRANSCRIPTION FACTORS
c. BCR GENE REARRANGEMENT
d. BCR STRUCTURE
e. GENE REARRANGEMENT
PROCESS
f. ALLELIC EXCLUSION
g. PROGRESSION TO NEXT STAGE
BCR STRUCTURE
107
Antigen-independent phase: PROgenitor-B CELL
a. contains light and heavy chain
b. heavy chain only
c. both
d. neither
| BCR STRUCTURE
a. contains light and heavy chain
108
Antigen-independent phase: PROgenitor-B CELL
a. constant regions: epitope specificty
b. variable regions: intracellular signalling and activation
c. both
d. neither
d. neither (reverse)
variable regions: epitope specificty
constant regions: intracellular signalling and activation
109
# Antigen-independent phase: PROgenitor-B CELL
t OR f
Rearrabgement occurs in stepwise manner
T
110
# Antigen-independent phase: PROgenitor-B CELL
* Enzymes bring together V, D, and J segments by looping out intervenin DNA
* Terminal deoxynucleotidyl transferase incorporates random nucleotides into joints
* Results in unique BCR genes not found in the genome
a. SIGNALING
b. TRANSCRIPTION FACTORS
c. BCR GENE REARRANGEMENT
d. BCR STRUCTURE
e. GENE REARRANGEMENT
PROCESS
f. ALLELIC EXCLUSION
g. PROGRESSION TO NEXT STAGE
| WHAT SPECIFIC PROCESS
e. GENE REARRANGEMENT
PROCESS
111
# Antigen-independent phase: PROgenitor-B CELL
* Once heavy-chain rearrangement is
completed successfully on one
chromosome, expression of the
**heavy-chain gene on the opposite chromosome is silenced**
a. SIGNALING
b. TRANSCRIPTION FACTORS
c. BCR GENE REARRANGEMENT
d. BCR STRUCTURE
e. GENE REARRANGEMENT
PROCESS
f. ALLELIC EXCLUSION
g. PROGRESSION TO NEXT STAGE
| WHAT SPECIFIC PROCESS
ALLELIC EXCLUSION
112
# Antigen-independent phase: PROgenitor-B CELL
* Pro-B cells must undergo successful heavy-chain gene rearrangement to progress to the next stage of differentiation
a. SIGNALING
b. TRANSCRIPTION FACTORS
c. BCR GENE REARRANGEMENT
d. BCR STRUCTURE
e. GENE REARRANGEMENT
PROCESS
f. ALLELIC EXCLUSION
g. PROGRESSION TO NEXT STAGE
| WHAT SPECIFIC PROCESS
PROGRESSION TO
NEXT STAGE
113
# Antigen-independent phase: PREcursor-B CELL
* Heavy chains accumulate in cytoplasm
* Some **heavy chains travel to cell surface** and combine with surrogate light chain, Ig-α, and Ig-β to form pre-B cell receptor (pre-BCR)
a. CHARACTERISTICS
b. PRE-BCR
c. LIGHT-CHAIN GENE
REARRANGEMENT
d. IMMUNOGLOBULIN
FORMATION
e. TRANSITION TO
IMMATURE B CELL
| SELECT
CHARACTERISTICS
114
# Antigen-independent phase: PREcursor-B CELL
* Comprised of heavy chain, surrogate light chain, Ig-α, and Ig-β
* Signals cell to undergo several rounds of **cell division**, resulting in clones of cells with identical heavy chain
a. CHARACTERISTICS
b. PRE-BCR
c. LIGHT-CHAIN GENE
REARRANGEMENT
d. IMMUNOGLOBULIN
FORMATION
e. TRANSITION TO
IMMATURE B CELL
PRE-BCR
115
# Antigen-independent phase: PREcursor-B CELL
* Begins simultaneously with pre-BCR appearance
* Involves rearrangement of κ or λ light-chain genes
* V, J, and **constant regions are stitched together**
a. CHARACTERISTICS
b. PRE-BCR
c. LIGHT-CHAIN GENE
REARRANGEMENT
d. IMMUNOGLOBULIN
FORMATION
e. TRANSITION TO
IMMATURE B CELL
LIGHT-CHAIN GENE
REARRANGEMENT
116
# Antigen-independent phase: PREcursor-B CELL
* Successfully rearranged light chains
combine with heavy chains to form
immunoglobulins (IgM)
* Immunoglobulins are fastened together by **disulfide bonds** and travel to cell surface
a. CHARACTERISTICS
b. PRE-BCR
c. LIGHT-CHAIN GENE
REARRANGEMENT
d. IMMUNOGLOBULIN
FORMATION
e. TRANSITION TO
IMMATURE B CELL
IMMUNOGLOBULIN
FORMATION
117
# Antigen-independent phase: PREcursor-B CELL
* Appearance of functional B cell receptor (BCR) on cell surface signifies entry into immature B cell stage
a. CHARACTERISTICS
b. PRE-BCR
c. LIGHT-CHAIN GENE
REARRANGEMENT
d. IMMUNOGLOBULIN
FORMATION
e. TRANSITION TO
IMMATURE B CELL
TRANSITION TO
IMMATURE B CELL
118
# Antigen-independent phase: ImMature b cell
* Expression of **functional IgM** B cell receptor (BCR) on cell surface
**Random specificity** of BCR due to gene rearrangement
* High likelihood of self-reactive BCRs
a. CHARACTERISTICS
B. NEGATIVE SELECTION
C. SURFACE MARKERS
D. MATURE B CELL
| SELECT
CHARACTERISTICS
119
# Antigen-independent phase: ImMature b cell
* CD21: receptor for complement component C3
* CD40: important for interaction with CD4+ T helper (Th) cells
* Class II MHC molecules: essential for
antigen presentation to CD4+ Th cells
a. CHARACTERISTICS
B. NEGATIVE SELECTION
C. SURFACE MARKERS
D. MATURE B CELL
SURFACE
MARKERS
120
# Antigen-independent phase: ImMature b cell
* receptor for complement
component C3d
| SURFACE MARKERS
CD 21
121
# Antigen-independent phase: ImMature b cell
* important for interaction with CD4+ T helper (Th) cells
| SURFACE MARKERS
CD40
122
# Antigen-independent phase: ImMature b cell
* essential for
antigen presentation to CD4+ Th cells
| SURFACE MARKERS
Class II MHC molecules
123
# Antigen-independent phase: ImMature b cell
* Expresses functional IgM BCR
* **Survives negative selection**
* Displays B cell markers (CD21,
CD40, MHC)
Exits bone marrow and travels to
spleen for further development
a. CHARACTERISTICS
B. NEGATIVE SELECTION
C. SURFACE MARKERS
D. MATURE B CELL
MATURE B CELL
124
# Antigen-independent phase: Mature b cell
* Follicular B cells
* Marginal-zone B cells
a. TWO TYPES OF MATURE B CELLS
b. CHARACTERISTICS OF MATURE B
CELLS
c. BCR SIGNALING
| SELECT
TWO TYPES OF MATURE B CELLS
125
# Antigen-independent phase: Mature b cell
* Recirculate between blood and secondary lymphoid organs
* Respond to antigens with help from CD4+ follicular helper (Tfh) cells
* Form immunologic memory
| TWO TYPES OF MATURE B CELLS
Follicular B cells
126
# Antigen-independent phase: Mature b cell
* Remain in the spleen
* Respond quickly to blood-borne pathogens
* Produce IgM-secreting plasma cells
without Tfh cell help
| TWO TYPES OF MATURE B CELLS
Marginal-zone B cells
127
# Antigen-independent phase: Mature b cell
* Express IgM and IgD B cell receptors
(BCRs) with the same antigenic specificity
* Presence of both IgM and IgD on the
cell membrane signifies a mature B
cell
a. TWO TYPES OF MATURE B CELLS
b. CHARACTERISTICS OF MATURE B
CELLS
c. BCR SIGNALING
b. CHARACTERISTICS OF MATURE B
CELLS
128
# Antigen-independent phase: Mature b cell
* Binding of BCR to specific antigeninitiates intracellular signaling cascade
* Signals drive B cell to enter proliferative stage, producing antibody-secreting plasma cells and
memory B cells (for follicular B cells)
a. TWO TYPES OF MATURE B CELLS
b. CHARACTERISTICS OF MATURE B
CELLS
c. BCR SIGNALING
BCR SIGNALING
129
# Antigen-independent phase: Mature b cell
T or F
Follicular B cells require Tfh cell help,
while marginal-zone B cells do not
T
130
# Antigen-independent phase: Mature b cell
T or F
Marginal-zone B cells form immunologic
memory, while Follicular B cells
do not
F (reverse)
**Follicular B cells form immunologic
memory**, while marginal-zone B cells
do not
131
* Reflects their role as antibody-production factories
* Abundant cytoplasLittle surface immunoglobulin
* Oval-shaped nuclei with clumped, dark-staining chromatin
* Ample endoplasmic reticulum and well-defined Golgimic immunoglobulin
* Little surface immunoglobulin
Plasma Cell
132
Resident plasma cells are found in what 2 locations?
Bone marrow, Germinal centers of peripheral lymphoid organs
133
Plasma cells in BM or Plasma cells in other tissues?
* Survive with support from stromal cells
* Receive cytokine stimulation
* Produce antibodies continually
Plasma cells in BM
134
Surface marker found on plasma cells?
CD138
135
* are populations of long-lived T or B cells that
have been stimulated by antigen.
* They can make a quick response to a previously encountered antigen.
Memory B cell/T cell
136
* carry surface IgG as their antigen receptor
Memory B cells
137
* express the CD45RO variant of the
leukocyte common antigen and increased levels of cell-adhesion molecules (CAMs), chemical mediators involved in inflammatory processes throughout the body
Memory T cells
138
Plasma cells in BM or Plasma cells in other tissues?
* Produce antibody for a short time then die
Plasma cells in otehr tissues
