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Pathogens Flashcards

1
Q

Is the INNATE fast or slow?

A

Fast.

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2
Q

Does the INNATE have diversity?

A

No, it has no diversity or specificity.

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3
Q

Is the INNATE specialized?

A

No, the INNATE is general and not specialized nor specific.

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4
Q

Does the INNATE contain memory?

A

No, the INNATE has no memory,

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5
Q

Is the ADAPTIVE fast or slow?

A

Slow.

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6
Q

Is the ADAPTIVE diverse?

A

Yes, the ADAPTIVE is diverse.

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7
Q

Is the ADAPTIVE specialized?

A

Yes, the ADAPTIVE is specialized and specific.

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8
Q

Does the ADAPTIVE contain memory?

A

Yes, the ADAPTIVE contains memory.

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9
Q

What role does the INNATE take?

A

It is the first line of defense.

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10
Q

What role does the ADAPTIVE take?

A

It offers selective and precise protection.

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11
Q

Antigen definition…

A

Protein or carbohydrate that engages the immune system and initiates an immune response.

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12
Q

Protein facts

A

Majority of antigens, may be pure proteins, glycoproteins or lipoproteins.

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13
Q

Polysaccharides facts

A

Pure polysaccharides or lipopolysaccharides.

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14
Q

Lipids facts

A

Non-immunogenic in general, but may assist in antigen-mediated immune activation. (NK, NKT cells)

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15
Q

Nucleic Acids facts

A

Usually poorly immunogenic, most effective when single-stranded or complexed with proteins.

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16
Q

Antigens recognized by specific antibody proteins or T-cell receptors are targets to which immune response?

A

These antigens serve as targets of the adaptive immune response.

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17
Q

Epitope

A

Antigenic determinant and actual molecular structure that interacts with a single antibody or T-cell receptor.

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18
Q

Types of Epitopes

A

Linear epitope: formed by a specific sequence and Conformational epitope: formed by a 3-D structure.

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19
Q

B-cell Epitopes

A

Region of antigen recognized by immunoglobulins/antibodies.

3-20 a.a. or sugar residues.

Limited to portions of the antigen that are accessible to the antibody.

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20
Q

T-Cell Epitopes

A

Region of antigen recognized by T-cell receptor
8-15 a.a. long
Recognized by T-cell receptor only after being processed and presented in association with an MHC protein. Limited to portions of the antigen that can bind to MHC proteins.

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21
Q

Important to remember that…

A

ONE ANTIGEN CAN HAVE MANY DIFFERENT EPITOPES.

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22
Q

Major histocompatibility complex (MHC) Principles

A

Control immune response to all protein antigens/ graft rejection.

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23
Q

Major histocompatibility complex (MHC) Principles

A

Polygenic: several different MHC I and II alleles, therefore every individual has a set of MHC molecules with different ranges of peptide binding specificities.

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24
Q

Major histocompatibility complex (MHC) Principles

A

Most polymorphic genes in the genome.
Potentially 8-9 million HLA I alleles: (40 000 + identified)
(2000+ HLA-A, 2000+ HLA-B, 1000+ HLA-DR variants).

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25
Genetics
aka “human leukocyte antigens” (HLA).
26
Genetics
CD8+ T-cells recognize MHC I HLA-A, HLA-B, HLA-C
27
Genetics
CD4+ T-cells recognize MHC II HLA-DR, HLA-DQ, HLA-DP
28
Genetics
MHC genes are co-dominantly expressed
29
Genetics
MHC haplotype: set of maternally- and paternally-derived MHC genes on each chromosome (3 MHCI, 3 MHCII from each parent – total of 12 make up your HLA “fingerprint”.
30
T-cell receptor responsibilities
Recognize foreign antigens presented by MHC proteins on the surface of host cells.
31
T-cell receptor responsibilities
The TcR repertoire (genetic diversity) of α/β T-cells allows for tremendous ability to recognize different antigens.
32
T-cell receptor responsibilities
TcRs have only 1 antigen binding site (BcR has 2).
33
T-cell receptor responsibilities
TcR are always membrane-bound (BcRs are also secreted as Ab).
34
T-cell expresses approximately how many identical TcRs?
Approximately 30,000 identical TcRs.
35
Professional Ag-presenting cells... (there are 3)
Macrophages Dendritic cells B-cells
36
Macrophages Cells Stimulation
stay in tissues, intitate inflammation.
37
Macrophages Cells Phagocytosis
focus on destroying cells/ remove apoptotic cells.
38
Macrophages Cells Other Roles
tissue repair, maintenance (lifetime), various tissue specific.
39
Dendritic Cells Stimulation
change from sampling to migration (stim by inflammation signals).
40
Dendritic Cells Phagocytosis
focus on Micropinocytosis/ controlled proteolysis.
41
Dendritic Cells Other Roles
NO! (Antigen presentation only).
42
Dendritic Cells Lifespan
short lived (days-weeks) – die after effector function.
43
Macrophages Cells Lifespan
long lived (years in tissue) – can be shorter (days) if activated.
44
APC – Sentinels
Exists in 2 stages; "patrolling mode" and “Antigen presentation mode”
45
APC – Sentinels "patrolling mode"
First line of defense.
46
APC – Sentinels "patrolling mode"
Found just below the skin.
47
APC – Sentinels "patrolling mode"
Slow turnover, regularly sampling environment.
48
APC – Sentinels Antigen presentation mode”
Upregulation of antigen presentation molecules (MHCI/II).
49
APC – Sentinels Antigen presentation mode”
Increased co-activation factors (membrane and secreted).
50
APC – Sentinels Antigen presentation mode”
Increased sampling of environment.
51
APC – Sentinels Antigen presentation mode”
Engulfed invaders are not only destroyed, processed pieces are displayed to activate Lymphocytes.
52
APC – Sentinels Antigen presentation mode”
APC “leaving” the periphery also produce cytokines to attract monocytes and stimulate them to become dendritic cells – short lifespan 5-7 days.
53
PRR (Pattern Recognition Receptors) PAMP/DAMP Expression. Various Pattern recognition receptors features.
TLR-Toll like receptor RLR-Rig like receptor (IFNα/β) NLR-NOD like receptor (inflammatory) Lectin like receptors
54
Important to note...
All of the above are expressed in various compartments based on where they will potentially encounter their ligands.
55
Peripheral Dendritic cells: (myeloid), Roles of APC vary with location
travel from peripheral site to LN to present antigens to T cells (can be monocyte derived).
56
Resident/ Follicular Dendritic cells (plasmacytoid and lymphoid), Roles of APC vary with location.
stay in LN to sample lymph for opsonized antigens to present to B cells. Antigen presentation is not MHC restricted (held on the surface for display to B cells – some macrophages can also do this) Like a Christmas tree ☺ and activate T/B cells in LN.
57
Macrophages, Roles of APC vary with location
stay at sites of infection/inflammation and support the fight at the site of infection, also re-stimulate T cells that have arrived from LN at peripheral sites of inflammation.
58
B cells, Roles of APC vary with location
stay in LN and present antigen/activate CD4 T cells to support antibody production. -sample antigen specifically through BCR and present it to CD4 T cells.
59
General features of DCs, IMMATURE/QUIESCENT STATE
Routinely process and present antigen Express PRRs Express low levels of MHC I and II
60
General features of DCs, MATURE STATE
Increase antigen processing and presentation Increase MHC expression Express co-stimulatory molecules for T-cells B7.1, B7.2 (CD80/CD86) to bind ligands on T-cells (CD28 – activates; CTLA-4 – inhibits) Produce cytokines.
61
How are t-cells activated?
T cells are activated through high affinity TCR engagement with MHC/ peptide Complexes though Receptor activation: CD4/TCR:MHC class II CD8/TCR:MHC class I
62
T-cell CO-activation
provided by cytokines, secreted by activated APC
63
T-cell location and movement
Naïve T cells constantly circulate through LN for a match. Once they are stimulated, they leave to sites of inflammation.
64
Signals required for effective T cell activation (3 Signals)
Signal 1: MHC-peptide-TcR recognition (naïve and memory T-cells) Signal 2: co-stimulation recognition (naïve T-cells) Signal 3: cytokine signaling recognition (naïve and memory T-cells)
65
How long does Immunological Synapse take?
Takes about 4-10 hours
66
Immunological Synapse
Adhesion molecules bring APC And T cell together. MHC/peptide:TCR recognition Strengthens interaction Rearrangement of cytoskeleton and polarization of cell results in the Formation of the immunological synapse
67
Treg functions
Control/ dampen immune response Maintain tolerance to self antigens Prevent autoimmune disease
68
Some differentiated CD4 cells are not terminal
They can change with the course of the infection to respond to needs of the immune system dynamically And respond to both innate and adaptive controls.
69
How can a NAÏVE antigen-specific lymphocyte manage to contact its specific antigen, or encounter a helper cell with the appropriate antigen specificity?
The “dating bars of the body”– the Lymph nodes.
70
Secondary Lymphoid Organs
Lymph nodes Spleen Many “_ALT” Associated Lymphoid Tissues
71
Many “_ALT” Associated Lymphoid Tissues (3*)
GALT (gut-associated lymphoid tissue) Lamina propria, Peyer’s patches BALT (bronchial-associated lymphoid tissue) Respiratory epithelium MALT (mucosal-associated lymphoid tissue) Other diffuse mucosal sites, ex reproductive tract, small and large intestine (These organs share common structural and functional features).
72
How many lymphocytes enter the LN through the HEV each second
About 10,000
73
Role of the lymph node in the immune response
Specialized organ that facilitates the presentation of foreign antigen to the immune system.
74
Naïve cells
Have surface adhesion molecules for any secondary lymphoid organs. They stay in the circulation, if no match found after a couple of weeks/months - death by apoptosis.
75
Activated cells
have surface adhesion molecules that are expressed depending on where they were activated – tend to return to compartments they encountered antigen. Also carry adhesion molecules to direct them to sites of inflammation.
76
Activated B cells
Remain in the LN and cycle between germinal and follicular zones – replicating and getting T- cell help as they travel to T/B cell borders Some mature into plasma cells and exit the LN and take up residence in the LN medulla, Spleen or bone marrow where they produce large quantities of antibodies Some recirculate to other LN where they can be re-stimulated and undergo Somatic hypermutation and class switching.
77
What is MALT?
gut surveillance Lamina propria Peyer’s patches
78
Lamina Propria
connective tissue containing Lymphocytes and some germinal centers
79
Peyer’s patches
lymph node-like nodules in ILEUM, have HEV but no systemic Incoming lymphatics M cells – sample gut lumen, Endosomes transport antigens through M cells to Peyer’s patches B-cell follicles Subepithelial Dome – T cells, B cells, resident and monocyte derived DC.
80
Spleen Responsibilities
Filters the blood collects antigen from the blood and disposes of old red blood cells (in red pulp) Naïve T and B cells travelling in blood are retained in the white pulp which consists of PALS (periarterial lymphoid sheath) and B-cell corona. No lymphatic entry- resident dendritic cells screen the blood and bring antigens to B/ T cells zones. Important site for the induction of B-cell responses to blood-borne antigens. encapsulated bacteria (e.g. S. pneum., H. infl.)
81
Summary – Cell mediated Adaptive immunity
Invading pathogens which are recognized (by PRR), are attacked and engulfed by APC. Antigens are then processed by APC (DC), displayed by MHC surface molecules and transported to the LN Some DC are residents of the LN, where they are constantly monitoring lymph for opsonized antigens. Naïve T and B cells encounter their matching antigens, displayed by APC in LN Recognition of antigens bound by MHC molecules in addition to co-activation signals, stimulate naïve T cells to become effectors. In turn, Activated CD4 helper cells increase activity and survival of APC. Upon activation CD8 T cells exit LN to sites of inflammation Upon activation CD4 T cells are differentiated/ polarized by distinct cytokine signals from APC that are dependent on the threat encountered. Activated CDT 4 T-cells recirculate, or leave the LN to destination sites to support specific actions of other immune cells to direct/polarize the immune response (dendritic cells, T cells, B cells). Once the threat is eliminated, memory cells remain to provide long term, fast acting immunity against future assaults.

JJ (1 decks)

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