CH 15 - Adaptive Immune Response Flashcards
(83 cards)
1
Q
Adaptive immunity
A
Protection provided by immune responses that improve due to exposure to antigens
Involves B & T cells
2
Q
Antibody
A
Y-shaped protein that binds antigen
3
Q
Antigen
A
Molecule that reacts specifically with either antibody or antigen receptor on lymphocyte
4
Q
Antigen-presenting cells (APCs)
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Cells that can present exogenous antigens to T cells
Ex: dendritic cells, B cells, macrophages
5
Q
B cell
A
Type of lymphocyte programmed to make antibody molecules
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Q
Cell-mediated immunity (CMI)
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Immunity involving T-cell response
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Q
Clonal selection
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Process in which lymphocyte’s antigen receptor binds to antigen, allowing lymphocyte to multiply
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Q
Cytotoxic T cell
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Type of lymphocyte programmed to destroy infected or cancerous “self” cells
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Q
Dendritic cell
A
Cell type responsible for activating naive T cells
10
Q
Effector lymphocyte
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Differentiated descendant of an activated lymphocyte
Its actions help eliminate antigen
11
Q
Helper T cell
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Type of lymphocyte programmed to activate B cells & macrophages & assist other parts of adaptive immune response
12
Q
Humoral immunity
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Immunity involving B cells & antibody response
13
Q
Lymphocytes
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Group of WBCs (leukocytes) involved in adaptive immunity
Ex: B & T cells
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Q
Major histocompatibility complex (MHC) molecules
A
Host cell surface proteins that present antigens to T cell
15
Q
Plasma cell
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Effector form of B cell
Functions as antibody-secreting factory
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Q
Tc Cell
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Effector form of cytotoxic T cell
Induces apoptosis in infected/cancerous “self” cells
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Q
Th Cell
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Effector form of helper T cell
Activates B cells & macrophages & releases cytokines that stimulate other cells of the immune system
18
Q
Primary vs. Secondary Response
Primary Response
(Responding B cell , lag period, peak response, effect)
A
1st response to a particular antigen
- Naive B cells
May take week or more to develop
- Lag period of 10-12 days
(before Ab detection in blood)
- Peak response = 7-10 days
Activated B cells proliferate & differentiate into increasing #s of plasma cells in presence of Ag
- Slow/steady increase in Ab titer
Overtime, some B cells undergo changes enhancing immune response
Thymus-dependent & independent Ags
19
Q
Secondary Response
A
Immune system remembers pathogen on subsequent exposure
- Memory B cells
Enhanced & specific immune response
- Often limit invaders before noticeable harm done
- Lag period of 1-3 days
- Peak response = 3-5 days
- 100-1000x greater response than primary
- Higher Ab affinity
Vaccines exploit immunologic memory
Some memory B cells differentiate into plasma cells
- Rapid production of Abs
Thymus-dependent Ags
20
Q
Basis of Vaccine
A
Adaptive immunity
Ex: Milkmaids in the 1700s resistant to smallpox because exposed to cow pox 1st (related)
21
Q
Adaptive Immunity Divided Into:
A
- Humoral immunity
- Ab mediated (B cells)
- Eliminates EXTRACELLULAR pathogens - Cellular immunity
- T cell mediated
- Eliminates INTRACELLULAR pathogens
22
Q
Humoral Immunity:
Receptors/Cell Types
A
Mediated by B cells
(develop in bone marrow)
- B cell receptors (BCRs)
- Membrane-bound derivative of - Plasma cells
- Produce Abs when Ags bind BCRs - Memory cells
23
Q
Cellular Immunity:
Receptors/Cells Types
A
Mediated by T cells
(mature in thymus)
- T cell receptors (TCR)
- Help with Ag recognition - Cytotoxic (CD8+) T cells
- Helper (CD4+) T cells
24
Q
Lymphoid System
A
Collection of tissues/organs through which lymph travels
Includes:
1. Lymphatic vessels
2. Primary lymphoid organs
3. Secondary lymphoid organs
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Major Functions of Lymphoid System
1. Concentrate Ags into lymphoid organs
2. Circulate lymphocytes through lymphoid organs (so can interact with Ags)
3. Carry products of immune response to bloodstream/tissues (Abs & effector cells)
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Lymph
Extracellular fluid that bathes tissue (result of circulatory system)
Lymphatic vessels carry to body tissue
- Travels through vessels to lymph nodes
Contains:
1. Tissue products
2. Ags
3. Abs
4. Cells (lymphocytes)
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Areas where immune cells congregate at mucosa to defend against penetrating microbes:
MALT = mucosa-associated lymphoid tissue
SALT = skin-associated lymphoid tissue
GALT = gut-associated lymphoid tissue
BALT = bronchus-associated lymphoid tissue
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Primary Lymphoid Organs
Bone marrow & thymus
Location where stem cells destined to become B & T cells mature
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Secondary Lymphoid Organs
Sites where mature lymphocytes gather to encounter Ags
Includes:
1. Lymph nodes (trap Ags)
2. Spleen (trap foreign substances)
3. Tonsils
4. Adenoids
5. Appendix
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Antigens
Compounds that elicit Ab production
- "Ab generator"
- Any compound that reacts with Ab or antigen receptor on lymphocyte
Immunogens elicit immune response
- Proteins & polysaccharides = strong responses
May NOT elicit immune response
- Substances with MW < 10,000 da
- Lipids & nucleic acids
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Antigenic determinate (epitope)
Determines recognition of Ag
B & T cells recognize distinct epitopes
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Structure of Antibodies
Monomer = basic unit (IgG)
Made up of 4 chains of amino acids held together by disulfide bonds
- 2 chains = heavy
- 2 chains = light
Constant region (each heavy & light chain)
- Fc region binds Fc receptors
Variable region (each heavy & light chain)
- Unique to each Ab
- Antigen-binding site
- "Fab" region
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Protective Outcomes of Ab-Ag Binding
1. Neutralization
- Prevents toxin/virus from interacting with/entering cell
2. Immobilization & prevention of adherence
- Ab binds to cellular structures to interfere with function (ex: flagellum)
3. Agglutination & precipitation
- Clumping of bacterial cells by specific Ab (involves 2 binding sites)
- Makes phagocytosis easier
4. Opsonization
- Ab coats bacteria to enhance phagocytosis
5. Complement activation
- Ab binding surface of microbe triggers classical pathway
6. Antibody-dependent cell-mediated toxicity (ADCC)
- Fc region of multiple Abs binds cell (makes target)
- Substances secrete by nonspecific cytotoxic cells
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5 Classes of Abs:
1. IgM
2. IgG
3. IgA
4. IgD
5. IgE
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IgM
1st to respond to infection (produced 1st by B cells)
5-13% of Abs in circulation
Pentamer
- 5 monomer units joined together at constant region
- 10 binding sites (good for aggregates)
Monomer on surface of B cells
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Functions of IgM
1. Elicits classical complement cascade
(most efficient)
2. Agglutination & precipitation reactions
3. Produced during immune responses to T-independent antigens
4. Can be formed in fetus if infected in utero
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IgG
Dominant Ab in circulation (80-85%)
Monomer
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Functions of IgG
1. ONLY Ab that can cross placenta
2. Present in colostrum (protects babies after birth - absorbed by intestinal tract)
3. Ab of memory
4. Induces classical complement cascade
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IgA
10-13%
- Secreted form (sIgA) = majority
Monomer in serum
Dimer in secretions
- Monomer connected by J chain
- Ferried across epithelia by poly Ig receptor
- Secretory component protects Ab from proteolytic enzymes
Found in:
1. Breast milk
2. Mucus
3. Tears
4. Saliva
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Functions of IgA
1. Mucosal immunity
2. Protects babies from intestinal pathogens
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IgD
<1%
Monomer
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Function of IgD
Development & maturation of Ab response
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IgE
Barely detectable in circulation (<0.01%)
- Bound by FcRs of mast cells & basophils
Monomer
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Functions of IgE
1. Detect parasites/Ags & release granule contents (bound IgE)
2. Allergic reactions (anaphylaxis)
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Clonal Selection Theory
Clonal selection
- Antigen binds to only 1 preformed lymphocyte
- Initiates multiplication of Ag-specific lymphocyte
Clonal expansion
- Repeated cycles of cell division generates population of copied Abs
Without sustained stimulation, cells undergo apoptosis
- Curtails immune response
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Lymphocyte Characteristics
1. Immature
2. Naive
3. Activated
4. Effectors
5. Memory lymphocytes
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Immature Lymphocytes
NOT fully developed Ag-specific receptor
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Naive Lymphocytes
Most B cells
Have Ag receptor
Have NOT encountered Ag
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Activated Lymphocytes
Bound Ag
Able to proliferate
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Effector Lymphocytes
Descendants of activated lymphocytes
- Activation/differentiation pushed by T cells
Produce specific cytokines
Include:
1. Plasma cells
2. T helper cells
3. Cytotoxic T cells
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Memory Lymphocytes
Long-lived descendants of activated lymphocytes
Remembers Ag on subsequent exposure
Responsible for speed/effectiveness of secondary response
Continue producing Abs forever (permanent)
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B Lymphocytes & Ab Response
(steps of B cell activation)
1. Ag binds BCR
- Ag internalized by B cell & degraded
- Peptide fragments loaded into MHC II
- Peptides presented to T cells (APCs)
2. B cell needs confirmation from T helper cells
- Costimulatory or 2nd signal
3. Th cell recognizes Ag:
- Releases cytokines that activates B cells (differentiate/divide)
- Produce plasma cells & memory B cells
3. Th cell does NOT recognize Ag:
- Immune response may become "tolerant" to Ag
- No Abs produced
(even though BCRs engaged)
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Changes to Proliferating B Cells in Primary Response
1. Affinity maturation
2. Class switching
3. Formation of memory cells
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Affinity Maturation
B cells that bind Ag most tightly & for longest duration most likely to proliferate
- Others undergo apoptosis
Fine tunes quality of response (specificity)
Form of natural selection
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Class Switching
B cells initially programmed to differentiate into plasma cells
- Secrete IgM
Helper T cells produce cytokines that influence proliferation/differentiation
- Some B cells switch programming
- Secrete other classes of Abs
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Proliferation Cytokines
IL-2
IL-4
IL-5
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Differentiation Cytokines
IL-2
IL-4
IL-5
IFN-gamma
TNF-beta
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Antibody Diversity
Not enough DNA for separate genes to encode each Ab
1. Gene rearrangement
- Maturing B cells selects 3 segments & combines together (VDJ)
- V = 65
- D = 27
- J = 6
2. Imprecise joining
- Nucleotides added/deleted
3. Combinatorial associations
- Specific groupings of light & heavy chains
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Formation of Memory
Involves B cells that have undergone class switching
- Produce IgG (Ab of memory)
Circulate in body for years/lifetime
- Protect against specific Ags
Memory lymphocytes responsible for speed/effectiveness of 2ndary response
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T-dependent Ags
Compounds that evoke immune response ONLY with aid of T helper cells
Protein Ags
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T-independent Ags
Activate B cells WITHOUT helper T cells
Carbohydrates (polysaccharides) & lipids (LPS)
- Capsules = poor T-dependent response
BCRs bind Ag simultaneously for B cell activation (multiple engagement)
Immune systems of young children (~2 yr) respond poorly to T-independent Ags
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T Cell Receptors (TCRs)
T cells have multiple copies of TCRs
Receptors have variable sites of Ag binding (similar to Abs - recombination)
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Role of T cells
NEVER produce Abs
- Do NOT react with free Ag
Armed with effectors that interact directly with target cells
- Ag MUST be presented by APC
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Peptide-binding groove
Ag cradled in groove of major histocompatability complex molecule (MHC) during Ag presentation
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2 Types of MHC
1. MHC class I
- Binds endogenous Ag (inside cell)
- Engagement with CD8 cells
- Found on ALL body cells
- "Kill me" signal
2. MHC class II
- Binds exogenous Ag (outside cell)
- Engagement with CD4
- ONLY found on APCs
- Drives Ab response
66
T Lymphocytes - Ag Recognition & Response
1. Naive T cells recognize Ag presented by dendritic cell
2. Recognizes Ag presented & dendritic cell expresses co-stimulatory molecule
- Activated
- Proliferate & develop effector function
2. Recognizes Ag presented & dendritic cell NOT displaying co-stimulatory molecule
- Driven to apoptosis OR becomes unresponsive to Ags
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Endogenous Pathway
1. Endogenous Ag degraded by protease
2. Peptide transported to rough ER via TAP (transporter)
3. Class I MHC captures peptide & chaperons dissociate
4. Class I MHC-peptide transported from rough ER to Golgi complex to plasma membrane
68
Exogenous Pathway
1. Class II MHC alpha & beta bind invariant chain
- Blocking binding of endogenous Ag
2. MHC complex routed through Golgi to endocytic pathway compartments
3. Invariant chain degraded
- Leaving CLIP fragment
4. Exogenous Ag taken up, degraded, & routed to endocytic pathway compartments
5. HLA-DM mediates exchange of CLIP for Ag peptide
6. Class II MHC-peptide transported to plasma membrane
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Antigen Presenting Cells (APCs)
1. Dendritic cells
2. Macrophages
3. B lymphocytes
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Dendritic Cells:
APC Function
Ag uptake:
- Endocytosis
- Phagocytosis (Langerhans cells)
Activate:
1. Naive T cells
2. Effector T cells
3. Memory T cells
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Macrophages:
APC Function
Ag uptake:
- Phagocytosis
Activated macrophages activate:
1. Effector T cells
2. Memory T cells
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B lymphocytes:
APC Function
Ag uptake:
- Receptor-mediated endocytosis
Resting B cells activate:
1. Effector T cells
2. Memory T cells
Activated B cells activate:
1. Naive T cells
2. Effector T cells
3. Memory T cells
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2 Major Functional T Cell Populations
1. Cytotoxic T cells (Tc)
2. Helper T cells (Th)
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Cytotoxic T cells (Tc)
Proliferate & differentiate to destroy infected or cancerous "self" cells & in graft rejection
CD8 marker
Recognize MHC class I
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Helper T cells
Orchestrate immune response
- Multiply/develop into Th1-type & Th2-type
- Stimulate other T cells
Th1-type
- Activates cell-mediated immune responses & macrophages
Th2-type
- Activates humoral responses
CD4 marker
Recognize MHC class II
76
Functions of Tc (CD8) Cells
1. Induce apoptosis
- Self cells infected with virus/intracellular microbe
- Cancerous self cells
- Foreign cells involved with graft rejection
2. Secretes cytokines
77
Tc (CD8) Cells:
Mechanism of Action
Recognize MHC class I molecule loaded with peptide on nucleated target cell
Release pre-formed cytotoxin that induce lysis or apoptosis (perforin, proteases, granzymes)
Induces apoptosis through binding of Fas ligand (FasL) on activated CD8 T cell to Fas on target cell (engaging apoptotic receptor)
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Functions of Th (CD4) Cells
1. Orchestrate immune response
2. Role in cell activation
3. Role in macrophage activation
- Recognize macrophage with engulfed microbes resistant to killing
- Deliver cytokines that activate macrophages & induce more potent destructive mechanisms
- Macrophages fuse to form giant cell (granuloma) when cannot deal with microbial infection (prevents dissemination)
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Th (CD4) Cells:
Mechanism of Action (in B cell activation)
1. Recognize MHC class II
2. Deliver cytokines
3. B cell activated in response to cytokine stimulation (proliferation, class switching, formation of memory B cells)
80
Negative Selection:
"Self" Reactive B cells
Aka: clonal deletion
Process of eliminating B cells that bind "self" antigens
- Undergo apoptosis
Naive B cells that recognize Ag in secondary lymphoid tissue eliminated if do not receive 2nd signal from T helper cell
Failure leads to production of autoAbs (autoimmune disease)
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Selection of T cells
Negative selection
- "Self" reactive T cells
- Recognize/bind "self" Ags
- Undergo apoptosis
Positive selection
- ONLY T cells that recognize/bind MHC
- TCR recognizes peptide:MHC complex
82
Natural Killer (NK) Cells
Descend from lymphoid stem cells
Mediate lysis of host cells altered by:
1. Stress
2. Viral infection
3. Transformed into tumor cells (express less MHC I)
Expression of relatively high levels of MHC I on normal cells protects against NK-mediated killing
- Virus/pathogens that down-regulate MHC I targeted
Regulated by balance of positive signals (activating receptors) & negative signals (inhibitory receptors)
Involved in innate immunity
- Antibacterial
- Lipid Ags specific to tumor cells
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A group of interacting serum proteins that provide nonspecific defense mechanism is:
Complement
NOT:
- Interferon
- Glycoprotein
- Lysozyme
