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MOD1 > Chronic Inflammation, Cell-Mediated Type IV Hypersensitivity > Flashcards

Chronic Inflammation, Cell-Mediated Type IV Hypersensitivity Flashcards

1
Q

T cell receptors only see antigen presented on MHC complexes. Which type of T cell recognizes which type of MHC complex?

A
  • CD4+ helper T cells recognize MHC II
  • CD8+ cytoxotic T cell recognize MHC I
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2
Q

Describe the two steps for CD4+ activation

A
  1. APC phagocytoses and processes an extracellular antigen, and presents it via MHC II
  2. B7 on APC binds CD28 on CD4+ T cell
  • remember that 28/7 = 4
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3
Q

What are the two important factors Th1 secretes, and what do they activate?

A
  • IL-2 –> T cell growth, CD8+ T cell
  • IFN-γ –> macrophages

remember that Th1 is associated with cell-mediated response

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4
Q

What are the three important factors that Th2 secretes, and what do they activate?

A
  • IL-4 –> class switching to IgG and IgE
  • IL-5 –>
    • eosinophil chemotaxis and activation
    • B cell maturation into plasma cells
    • class switching to IgA
  • IL-10 –>
    • inhibits the Th1 phenotype

remember that Th2 is associated with the humoral response

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5
Q

Describe the two steps for CD8+ activation

A
  1. intracellular antigen processed, presented on MHC I
  2. IL-2 from CD4+ Th1 binds to receptor on CD8+
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6
Q

Two ways cytotoxic T cells kill once activated

A
  1. Secrete perforins that punch holes –> granzymes enter –> induce apoptosis
  2. Tc cells express **FasL, **and binds to Fas on target cell –> apoptosis
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7
Q

iWhat is the key mediator of apoptosis and what are three ways its activated?

A

CASPASE

  1. intrinsic mitrochondrial pathway
  2. extrinsic receptor pathway (Fas, TNF)
  3. CD8+ T cells dumping granyzme
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8
Q

Describe the main steps that need to occur for B cell activation

A
  1. Antigen binding IgM or IgD (naive B cell expresses these two on their surface)
  2. B cell eats antigen and presents it to CD4+ Th cell via MHC II; CD40 receptor on B cell binds CD40L on Th cell
  3. This interaction activates Th2 cell, which secretes IL-4 and IL-5 –> mediates B cell isotype class switching, hypermutation, and plasma cell maturatin

The T cell always has the ligand

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9
Q

Give 5 important examples of Non-caseating granulomatous inflammation

A
  1. Sarcoidosis
  2. Beryllium exposure
  3. Crohn disease
  4. Cat Scratch disease
    1. usually stellate shaped granuloma in neck
  5. Reaction to foreign material
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10
Q

While non-caseating granuloma is histologic hallmark for Crohn disease, what is the hallmark for Ulercerative colitis?

A

In UC, you see crypt abscess

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11
Q

3 important examples of caseating granulomatous inflammation

A
  1. Tuberculosis (AFB stain)
  2. Tuberculosis !!!!!!!!!!!!! always think this
  3. Fungal infections (GMS silver stain)
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12
Q

Which signal secreted from macrophages induces a T helper cell to differentiate into Th1 cell?

A

IL-12

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13
Q

List the three important steps in Granuloma formation

A
  1. MHC II on macrophage binds Th CD4+
  2. Macrophage secretes **IL-12 **
  3. In response, T helper cell differentiates into Th1, and secretes IFN- γ –> converts macrophages to epitheloid histiocytes

Note: this occurs in caseating and non-caseating

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14
Q

3 important traits of cell-mediated Type IV hypersenstiivity

A
  1. Type IV is initiated by T-lymphocytes
  2. It is NOT initiated by antibodies
  3. Delayed repsonse
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15
Q

What is the “double-edge sword” with cell-mediated response?

A

You get both immunity and hypersensitivity

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16
Q

In Hansen’s disease, you see two spectrums: Lepromatous and Tuberculoid. Explain the following for lepromatous

  • Antibody?
  • DTH?
  • Acid fast?
  • granuloma?
  • Type of T-cell
  • IL-12?
A

Lepromatous:

  • *Antibody:** yes
  • *DTH:** no
  • *Acid fast:** yes
  • *granuloma:** no
  • *Type of T-cell:** Th2
  • *IL-12:** no
17
Q

In Hansen’s disease, you see two spectrums: Lepromatous and Tuberculoid. Explain the following for Tuberculoid

Antibody?
DTH?
Acid fast?
granuloma?
Type of T-cell
IL-12?

A

_Tuberculoid _

  • *Antibody:** no
  • *DTH:** yes
  • *Acid fast:** no
  • *granuloma:** yes
  • *Type of T-cell:** Th1
  • *IL-12:** yes
18
Q

What is the “master switch” that determined whether or not you get an antibody response?

A

IL-12

  • secreted by macrophages
  • induces Th to differentiate into Th1
  • if naive Th doesn’t get signal, it will become Th2
19
Q

What is an iNKT cell? Where do you usually see them?

A
  • invariant natural killer cell
  • natural, innate immunity, not adaptive immune response
  • reacts with lipid antigens
  • found in patients with asthma and ulcerative colitis
20
Q

What are the two subsets of Type IV sensitivity?

A
  1. Cytokine-driven or “classical”
  2. Cytotoxic Lymphocytes
21
Q

List the main players in Cyotkine-driven Type IV hypersensitivity and their actions

A
  • CD4+ T helper cells
    • produces IFN-γ only AFTER stimulated by antigen
  • Macrophages convert to epitheloid histiocytes in response to IFN-γ
  • Macrophages then kill tissue
22
Q

Classic example of Cyotkine-driven Type IV hypersensitivity

A

Tuberculosis

23
Q

What is secondary TB and its cause?

A
  • reactivation of latent TB
  • due to compormised immune system (something that causes you to lose your delayed hypersensitivitiy)
    • HIV, steroids, diabetics, old age, cancer, immunosuppressant therapy
24
Q

List the main players in Cytotoxic T-lymphocyte (CTL) subset of Type IV hypersensitivity

A
  • CD8+ cytotoxic T cells recognizes antigen of cell it’s going to kill, forms a synapse
  • into synapse secretes: granules
    • contain perforin and granzymes
    • FasL on Tcand Fas on target cell
    • etc. etc.
25
Q

What makes CTL-1 (cytotoxic T lymphocyte) unique?

A

It secretes IFN-γ –> macrophage activation

This is usually secreted by Th1 cells!

Not all CTLs turn out to be CD8+ cells, some are CD4+ !

26
Q

Why have a CD4+ killer cell?

A
  • macrophages have MHC II which CANNOT be recognized by CD8+
  • CD4+ killer cell can recognize it and kill it
27
Q

What is the main cause of rapid replication of keratinocytes in Psoriasis?

A

Th 22 cells –> IL-22 –> cell replication stimulation –> target keratinocytes, induce proliferation, anti-apoptotic pathways, acanthosis, and parakeratosis

28
Q

IL-17

A
  • Th17 CD4+ cells make it
  • suddenly appear in some patients with psoriasis and induce acute inflammatory repsonse
29
Q

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Clinical presentation

Major player

A
  • cutaneous adverse druge reaction
  • causes severe, life-threatening skin reactions, blisters (even with good tx)
  • TEN is more severe form of SJS
  • Granulysin induces epidermal necrosis
    • 15 kDa granulysisn is found in separate vacuole, secreted separately
    • lacks perforin and granzyme B that are usually activated by cytolytic cells
30
Q

What are the two necessary signals for activation of Cytotoxic T cells?

A
  1. Pre-cytotoxic T cell CD8+ recognizes antigen on MHC I
  2. CD4+ Th1 releases IL-2, which binds to IL-2 receptor on CD8+ (has high affnity for IL-2 receptors)

once receives these signals, cytotoxic T cell is activated for killing

MOD1 (9 decks)

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