CH 15 - Adaptive Immune Response Flashcards

1
Q

Adaptive immunity

A

Protection provided by immune responses that improve due to exposure to antigens

Involves B & T cells

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2
Q

Antibody

A

Y-shaped protein that binds antigen

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3
Q

Antigen

A

Molecule that reacts specifically with either antibody or antigen receptor on lymphocyte

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4
Q

Antigen-presenting cells (APCs)

A

Cells that can present exogenous antigens to T cells

Ex: dendritic cells, B cells, macrophages

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5
Q

B cell

A

Type of lymphocyte programmed to make antibody molecules

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6
Q

Cell-mediated immunity (CMI)

A

Immunity involving T-cell response

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7
Q

Clonal selection

A

Process in which lymphocyte’s antigen receptor binds to antigen, allowing lymphocyte to multiply

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8
Q

Cytotoxic T cell

A

Type of lymphocyte programmed to destroy infected or cancerous “self” cells

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9
Q

Dendritic cell

A

Cell type responsible for activating naive T cells

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10
Q

Effector lymphocyte

A

Differentiated descendant of an activated lymphocyte

Its actions help eliminate antigen

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11
Q

Helper T cell

A

Type of lymphocyte programmed to activate B cells & macrophages & assist other parts of adaptive immune response

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12
Q

Humoral immunity

A

Immunity involving B cells & antibody response

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13
Q

Lymphocytes

A

Group of WBCs (leukocytes) involved in adaptive immunity

Ex: B & T cells

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14
Q

Major histocompatibility complex (MHC) molecules

A

Host cell surface proteins that present antigens to T cell

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15
Q

Plasma cell

A

Effector form of B cell

Functions as antibody-secreting factory

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16
Q

Tc Cell

A

Effector form of cytotoxic T cell

Induces apoptosis in infected/cancerous “self” cells

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17
Q

Th Cell

A

Effector form of helper T cell

Activates B cells & macrophages & releases cytokines that stimulate other cells of the immune system

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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

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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

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20
Q

Basis of Vaccine

A

Adaptive immunity

Ex: Milkmaids in the 1700s resistant to smallpox because exposed to cow pox 1st (related)

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21
Q

Adaptive Immunity Divided Into:

A
  1. Humoral immunity
    - Ab mediated (B cells)
    - Eliminates EXTRACELLULAR pathogens
  2. Cellular immunity
    - T cell mediated
    - Eliminates INTRACELLULAR pathogens
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22
Q

Humoral Immunity:
Receptors/Cell Types

A

Mediated by B cells
(develop in bone marrow)

  1. B cell receptors (BCRs)
    - Membrane-bound derivative of
  2. Plasma cells
    - Produce Abs when Ags bind BCRs
  3. Memory cells
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23
Q

Cellular Immunity:
Receptors/Cells Types

A

Mediated by T cells
(mature in thymus)

  1. T cell receptors (TCR)
    - Help with Ag recognition
  2. Cytotoxic (CD8+) T cells
  3. Helper (CD4+) T cells
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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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25
Q

Major Functions of Lymphoid System

A
  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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26
Q

Lymph

A

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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27
Q

Areas where immune cells congregate at mucosa to defend against penetrating microbes:

A

MALT = mucosa-associated lymphoid tissue

SALT = skin-associated lymphoid tissue

GALT = gut-associated lymphoid tissue

BALT = bronchus-associated lymphoid tissue

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28
Q

Primary Lymphoid Organs

A

Bone marrow & thymus

Location where stem cells destined to become B & T cells mature

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29
Q

Secondary Lymphoid Organs

A

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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30
Q

Antigens

A

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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31
Q

Antigenic determinate (epitope)

A

Determines recognition of Ag

B & T cells recognize distinct epitopes

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32
Q

Structure of Antibodies

A

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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33
Q

Protective Outcomes of Ab-Ag Binding

A
  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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34
Q

5 Classes of Abs:

A
  1. IgM
  2. IgG
  3. IgA
  4. IgD
  5. IgE
35
Q

IgM

A

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

36
Q

Functions of IgM

A
  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
37
Q

IgG

A

Dominant Ab in circulation (80-85%)

Monomer

38
Q

Functions of IgG

A
  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
39
Q

IgA

A

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

40
Q

Functions of IgA

A
  1. Mucosal immunity
  2. Protects babies from intestinal pathogens
41
Q

IgD

A

<1%

Monomer

42
Q

Function of IgD

A

Development & maturation of Ab response

43
Q

IgE

A

Barely detectable in circulation (<0.01%)
- Bound by FcRs of mast cells & basophils

Monomer

44
Q

Functions of IgE

A
  1. Detect parasites/Ags & release granule contents (bound IgE)
  2. Allergic reactions (anaphylaxis)
45
Q

Clonal Selection Theory

A

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

46
Q

Lymphocyte Characteristics

A
  1. Immature
  2. Naive
  3. Activated
  4. Effectors
  5. Memory lymphocytes
47
Q

Immature Lymphocytes

A

NOT fully developed Ag-specific receptor

48
Q

Naive Lymphocytes

A

Most B cells

Have Ag receptor

Have NOT encountered Ag

49
Q

Activated Lymphocytes

A

Bound Ag

Able to proliferate

50
Q

Effector Lymphocytes

A

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

51
Q

Memory Lymphocytes

A

Long-lived descendants of activated lymphocytes

Remembers Ag on subsequent exposure

Responsible for speed/effectiveness of secondary response

Continue producing Abs forever (permanent)

52
Q

B Lymphocytes & Ab Response
(steps of B cell activation)

A
  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
  4. Th cell does NOT recognize Ag:
    - Immune response may become “tolerant” to Ag
    - No Abs produced
    (even though BCRs engaged)
53
Q

Changes to Proliferating B Cells in Primary Response

A
  1. Affinity maturation
  2. Class switching
  3. Formation of memory cells
54
Q

Affinity Maturation

A

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

55
Q

Class Switching

A

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

56
Q

Proliferation Cytokines

A

IL-2

IL-4

IL-5

57
Q

Differentiation Cytokines

A

IL-2

IL-4

IL-5

IFN-gamma

TNF-beta

58
Q

Antibody Diversity

A

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
59
Q

Formation of Memory

A

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

60
Q

T-dependent Ags

A

Compounds that evoke immune response ONLY with aid of T helper cells

Protein Ags

61
Q

T-independent Ags

A

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

62
Q

T Cell Receptors (TCRs)

A

T cells have multiple copies of TCRs

Receptors have variable sites of Ag binding (similar to Abs - recombination)

63
Q

Role of T cells

A

NEVER produce Abs
- Do NOT react with free Ag

Armed with effectors that interact directly with target cells
- Ag MUST be presented by APC

64
Q

Peptide-binding groove

A

Ag cradled in groove of major histocompatability complex molecule (MHC) during Ag presentation

65
Q

2 Types of MHC

A
  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
Q

T Lymphocytes - Ag Recognition & Response

A
  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
  3. Recognizes Ag presented & dendritic cell NOT displaying co-stimulatory molecule
    - Driven to apoptosis OR becomes unresponsive to Ags
67
Q

Endogenous Pathway

A
  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
Q

Exogenous Pathway

A
  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
69
Q

Antigen Presenting Cells (APCs)

A
  1. Dendritic cells
  2. Macrophages
  3. B lymphocytes
70
Q

Dendritic Cells:
APC Function

A

Ag uptake:
- Endocytosis
- Phagocytosis (Langerhans cells)

Activate:
1. Naive T cells
2. Effector T cells
3. Memory T cells

71
Q

Macrophages:
APC Function

A

Ag uptake:
- Phagocytosis

Activated macrophages activate:
1. Effector T cells
2. Memory T cells

72
Q

B lymphocytes:
APC Function

A

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

73
Q

2 Major Functional T Cell Populations

A
  1. Cytotoxic T cells (Tc)
  2. Helper T cells (Th)
74
Q

Cytotoxic T cells (Tc)

A

Proliferate & differentiate to destroy infected or cancerous “self” cells & in graft rejection

CD8 marker

Recognize MHC class I

75
Q

Helper T cells

A

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
Q

Functions of Tc (CD8) Cells

A
  1. Induce apoptosis
    - Self cells infected with virus/intracellular microbe
    - Cancerous self cells
    - Foreign cells involved with graft rejection
  2. Secretes cytokines
77
Q

Tc (CD8) Cells:
Mechanism of Action

A

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)

78
Q

Functions of Th (CD4) Cells

A
  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)
79
Q

Th (CD4) Cells:
Mechanism of Action (in B cell activation)

A
  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
Q

Negative Selection:
“Self” Reactive B cells

A

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)

81
Q

Selection of T cells

A

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
Q

Natural Killer (NK) Cells

A

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

83
Q

A group of interacting serum proteins that provide nonspecific defense mechanism is:

A

Complement

NOT:
- Interferon
- Glycoprotein
- Lysozyme