Lecture 3 Flashcards

(71 cards)

1
Q

Describe in brief the adaptive immunity in a nutshell.

A

Specific host defenses that are mediated by B and T cells following exposure to antigens and exhibit diversity and memory.

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2
Q

Why do some animals only have an innate immune system?

A

These animals likely don’t live long and have a great deal of offspring - like flies.

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3
Q

What are the shortcomings of the innate immunity and why?

A

Non specific - similar response for all PRRs
Poor regulation - little control
Poor amplification - response magnitude mostly equal
Lack of self discrimination - results in harm to self
Short duration
No memory

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4
Q

Name some different potential immune system triggers.

A
Bacteria
Fungus
Parasites
Viruses
Toxins
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5
Q

What are the four hallmarks of the adaptive immunity?

A

Specificity
Memory
Specialization
Nonreactivity to self antigens

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6
Q

What is the significance of specificity in the adaptive immunity?

A

Ability to recognize and respond to many different microbes

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7
Q

What is the significance of memory in the adaptive immunity?

A

Enhanced responses to recurrent or persistent infections.

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8
Q

What is the significance of specialization in the adaptive immunity?

A

Responses to distinct microbes are optimized for defense against these microbes

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9
Q

What is the significance of non reactivity to self antigens in the adaptive immunity?

A

Prevents injurious immune responses against host cells and tissues

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10
Q

What are the two types of adaptive immunity?

A

Cell mediated and humoral

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11
Q

What are the major cell types of the adaptive immunity? Which cells belong to those groups?

A

Lymphocytes - B & T cells

APCs - DCs, B cells, and macrophages

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12
Q

Where to T cells mature?
What receptors do they have?
What do T cells recognize on other cells?

A

Thymus
TcRs
MHC class I and II

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13
Q

MHC I is expressed where? What is it absolutely necessary for?

A

On all nucleated cells

Necessary for CD8+ T cell activation

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14
Q

MHC II is expressed where? What is it absolutely necessary for?

A

APCs

Necessary for CD4+ T cell activation

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15
Q

Name four types of T cells

A

Helper cells
Cytotoxic cells
Memory cells
Regulatory cells

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16
Q

Describe T helper cells and name their CD#

A

CD4+
MHC II restricted
Stimulate B and T cells

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17
Q

Describe T cytotoxic cells and name their CD#

A

CD8+
MHC I restricted
Further differentiate into cytotoxic T lymphocytes

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18
Q

What CD#s are memory T cells?

Regulatory T cells?

A

CD4+ and CD8+

CD4+ and CD25+

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19
Q

Describe T cell positive selection

A

Positive selection keeps T cells that have TcRs that are able to recognize MHC molecules.

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20
Q

Describe T cell negative selection

A

Negative selection removes t cells that can recognize self antigen in MHC molecules

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21
Q

What is the difference between + and - T cell selection?

A

Positive keeps cells reactive to MHC

Negative kills cells reactive to self

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22
Q

Where to B cells mature?
What is the B cell receptor?
How do B cells differentiate?
What kind of progeny do B cells leave behind?

A

Bone marrow
BcRs - aka membrane bound Ig
Specific Ag binding triggers division and differentiation
Plasma cells and memory B cells

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23
Q

Briefly describe the B cell selection process.

A

+ and - selection in the bone marrow
Selection is not MHC dependent
Binding and affinity are more important

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24
Q

Briefly describe APCs.

What is their function?

A

APCs are cells with the potential to capture, process, and present Ag to T cells.
APCs provide Ag to T cells as well as provide a second signal to T cells leading to proper activation (proliferation, differentation, and effector activities)

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25
What are the keys to the function of APCs?
Expression of MHC I and II on surface Ag internalization and degradation Co-stimulatory molecules expression
26
Define epitope.
A motif of conformational or primary sequence on an antigen that is recognized by B or T cells
27
What kind of epitopes do T cells recognize? | What kind of epitopes do B cells recognize?
MHC associated linear peptides | Conformational epitopes
28
What are the major molecules involved in Ag recognition?
``` BcRs TcRs MHC I MHC II CD4/CD8 co-receptors ```
29
Describe the clonal selection theory.
Clonal selection states that there are already lymphocytes with the right receptors for antigens and that the binding of a lymphocyte with the right antigen causes it to be 'selected'. Selection by Ag results in huge clonal expansion of the lymphocyte with the same receptors.
30
What are the steps to clonal selection?
Lymphocyte clones mature in lymphoid organs without Ag Clones of mature lymphocytes enter lymphoid tissues Ag specific clones are activated by Ag Ag specific immune responses occur
31
What are the two signals required for lymphocyte activation?
``` Specific recognition of antigen (via TcR or BcR) Non specific (via microbial molecules from APC or from the microbe itself [LPS/CpG etc.]) ```
32
What happens when a lymphocyte gets only a signal from a TcR/BcR but no non specific microbial molecule? Why?
It becomes anergic and gets deleted via apoptosis. | So that it cannot be over reactive and react to self. It's clearly not working properly
33
What are the five phases of the adaptive immune response? | What happens in these phases?
Recognition - Naive lymphocytes are contacted Activation - Activation, expansion, and differentiation Effector - Elimination of Ag via humoral/cell mediation Decline/homeostasis - Apoptosis Memory - surviving cells remain for memory
34
Which immune system can mount specific targetet responses to foreign Ags without responding to self?
Adaptive, duh
35
How is the adaptive immune system able to avoid reacting to self? Why is this important?
Early and continuous presence of self antigens | For self-tolerance and control of autoimmunity
36
Briefly describe the danger vs non-danger model of the adaptive immune system.
This states that the immune system does not descriminate between self and non-self but only is interested in responding to dangers (molecular patterns).
37
What are the key differences between the self-nonself model and the danger model?
Self-nonself is constantly looking for intruders to which to respond while danger only acts during emergency. Like comparing COPs to fire fighters
38
By what is cell mediated immunity conferred? | Describe it briefly.
T cells | It is cell dependent, modulates humoral immunity, and has cytotoxic T cells
39
Briefly describe how helper T cells are differentiated.
Naive CD4+ T cells get IL-2 and are activated by APCs If activated T cells get further influenced by... Activated DCs secreting IL-12: they become Th1 cells Activated by IL-4 from other cells: they become Th2s
40
What are the key differences between Th1 and Th2 cells?
``` Cytokines produced Cytokine receptor expression Chemokine receptor expression Ligands for E- and P- selectin Antibody isotypes stimulated Macrophage activation capabilities ```
41
Which cell, Th1 or Th2 produces cytokines IFNgamma, IL-2, and TNF?
Th1 (not Th2)
42
Which cell, Th1 or Th2, has cytokine receptors for Il-12R beta chain and IL-18R?
Th1 (not Th2)
43
What types of antibodies do Th1s stimulate?
IgG2a (mouse)
44
What types of antibodies do Th2s stimulate?
IgE IgG1 (mouse) IgG4 (humans)
45
Which cell type, Th1 or Th2, can stimulate macrophages?
Th1
46
After Th1 cells become differentiated, what do they secrete what what is the end result?
They secrete IFNgamma which affects macrophage activation and aids in complement binding and opsonizing anitibodies. End result is increased macrophage activation/microbial killing and increased opsonization/phagocytosis.
47
After Th2 cells become differentiated, what do they secrete what what is the end result?
They secrete IL-4 and IL-5. IL-4 helps B cells secrete IgE and ends in mast cell degranulation. IL-5 helps eosinophils activate and recognize parasites.
48
Describe the short list of mechanisms of CD8+ T cell activation.
``` Ag recognition and conjugate formation CTL activation CTL granule exocytosis Killing of target cell Granzymes enter through perforin holes and activate caspases inside. ```
49
What are three lesser known types of T cells?
Th17s Tregs Tfh cells
50
How is humoral immunity conferred? On what is it dependent? Which cells are involved?
Via serum (cell free) Antibody dependent B cells produce antibodies
51
What are B cells main function? | What is the B cells receptor aka?
Antibody production | Antibody
52
What are the differences between TcRs and BcRs?
BcRs recognize native intact protein in conformation and can be secreted at high concentration. TcRs recognize portions of linear epitopes and are membrane bound.
53
What are the five main types of antibodies? What are these families also known as (as a group)?
``` Isotypes IgM IgG IgE IgD IgA ```
54
What are the four effector mechanisms of humoral immunity?
Neutralization Antibody dependent cytolysis opsonization complement activation
55
Describe the neutralization of humoral immunity?
Binding to toxins/pathogens to block interactions with target cell receptors
56
Describe the antibody dependent cytolysis of humoral immunity?
Binding of Ab couples pathogen to a cell with the capacity to destroy it
57
Describe the opsonization of humoral immunity?
Ab coated particles are easier and more palatable for phagocytes to ingest.
58
Describe the complement activation of humoral immunity?
Leads to release of inflammatory mediators, deposition of opsonins, and direct lysis of microbes
59
What is ADCC? What is the result of this?
Antibody dependent cellular cytotoxicity. Kills antibody coated cells Kills helminths/parasites via eosinophils
60
Describe briefly the steps of Ab-mediated opsonization and phagocytosis of microbes.
``` Opsonization of microbe by IgG Binding of opsonized microbes to phagocyte by Fc receptors Fc receptor signals activate phagocyte Phagocytosis of microbe Killing of injected microbe ```
61
In antibody mediated complement activities, how do the following three scenarios work and waht is their end result? Opsonization and phagocytosis Complement mediated cytolysis Stimulation of inflammatory reactions
C3b binds to microbe which is recognized by CR1 and microbe is phagocytosed. C3b binds to microbe which causes the membrane to form a MAC (membrane attack complex) = osmotic lysis of microbe. C3b binds to microbe and C3a leaves to recruit activation of leucocytes = descruction by leukocyte
62
What is the immunologic memory? What does immunologic memory reflect? Immunologic memory is the hallmark of _____.
Ability of the immune system to respond more rapidly and effectively to pathogens that have been encountered previously - either by infection/vaccination. Reflects the pre-existence of clonally expanded lymphocytes with specificity for that antigen. Adaptive immunity.
63
Initial response to an antigen will cause B cells to release how many Ag? How about secondary responses? How much time does the first response take? Second response?
10^1 ish 10^4 Between 7-14 days 1-3 days to begin, 10 days for full 10^4 reaction
64
What are the factors that make immunological memory so effective?
``` More responder cells available More efficient Ag recognition/activation Rapid/effective migration to tissues/lymph nodes More effective function Longer lasting ```
65
What are the differences in the innate and adaptive immune systems related to.... 1. Receptors 2. Kinetics/speed 3. Regulation 4. Amplification 5. Self/nonself discrimination 6. Duration 7. Memory
Innate -- Adaptive 1. Primitive/broad -- Highly specific receptors (B&T) 2. Fast (hours-days) -- Slow (days-weeks) 3. May or may not -- Regulated highly 4. Insignificant -- Huge amplification 5. May or may not -- Very good at discrimination 6. Short (days) -- Long (months/years) 7. Non existant -- Excellent memory
66
How does the innate immunity shape the adaptive immunity? | Give examples for each.
Innate imme cells participate at both priming and effector phases of adaptive immunity. Macros and DCs present Ag to T cells IFNgamma prod. by NK cells activates macros NK cells can directly lyse infected cells Innate immune response generates molecules that act as second signals for B and T cell activation. APCs express costimulatory molecules Prod of cytokines (ILs 1, 2, 4, 10, 12, TNFalpha, IFNgamma, etc.)
67
What is the evolutionary need for adaptive immunity?
Self/nonself discrimination, specificity, amplification, regulation, and memory.
68
Describe how T and B cells mediate adaptive immunity.
T cells: cell-mediated B cells: humoral Innate immune cells also participate (macros, DCs, NKs)
69
Describe the effector mechanisms of the adaptive immunity.
Cell mediated immunity: direct cytotoxicity and prod of cytokines to control intracellular pathogens and tumors. Humoral immunity: by antibodies via neutralization, ADCC, opsonization, and complement activation
70
How are T cells activated?
Specific recognition of peptide/MHC complex (signal1) and costimulatory signals by APC (signal 2)
71
How are B cells activated?
Recognize native proteins (signal 1). May or may not require signal 2 from CD4+ T cells.