Chronic Inflammation, Cell-Mediated Type IV Hypersensitivity Flashcards
T cell receptors only see antigen presented on MHC complexes. Which type of T cell recognizes which type of MHC complex?
- CD4+ helper T cells recognize MHC II
- CD8+ cytoxotic T cell recognize MHC I
Describe the two steps for CD4+ activation
- APC phagocytoses and processes an extracellular antigen, and presents it via MHC II
- B7 on APC binds CD28 on CD4+ T cell
- remember that 28/7 = 4
What are the two important factors Th1 secretes, and what do they activate?
- IL-2 –> T cell growth, CD8+ T cell
- IFN-γ –> macrophages
remember that Th1 is associated with cell-mediated response
What are the three important factors that Th2 secretes, and what do they activate?
- 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
Describe the two steps for CD8+ activation
- intracellular antigen processed, presented on MHC I
- IL-2 from CD4+ Th1 binds to receptor on CD8+
Two ways cytotoxic T cells kill once activated
- Secrete perforins that punch holes –> granzymes enter –> induce apoptosis
- Tc cells express **FasL, **and binds to Fas on target cell –> apoptosis
iWhat is the key mediator of apoptosis and what are three ways its activated?
CASPASE
- intrinsic mitrochondrial pathway
- extrinsic receptor pathway (Fas, TNF)
- CD8+ T cells dumping granyzme
Describe the main steps that need to occur for B cell activation
- Antigen binding IgM or IgD (naive B cell expresses these two on their surface)
- B cell eats antigen and presents it to CD4+ Th cell via MHC II; CD40 receptor on B cell binds CD40L on Th cell
- 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
Give 5 important examples of Non-caseating granulomatous inflammation
- Sarcoidosis
- Beryllium exposure
- Crohn disease
- Cat Scratch disease
- usually stellate shaped granuloma in neck
- Reaction to foreign material
While non-caseating granuloma is histologic hallmark for Crohn disease, what is the hallmark for Ulercerative colitis?
In UC, you see crypt abscess
3 important examples of caseating granulomatous inflammation
- Tuberculosis (AFB stain)
- Tuberculosis !!!!!!!!!!!!! always think this
- Fungal infections (GMS silver stain)
Which signal secreted from macrophages induces a T helper cell to differentiate into Th1 cell?
IL-12
List the three important steps in Granuloma formation
- MHC II on macrophage binds Th CD4+
- Macrophage secretes **IL-12 **
- 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
3 important traits of cell-mediated Type IV hypersenstiivity
- Type IV is initiated by T-lymphocytes
- It is NOT initiated by antibodies
- Delayed repsonse
What is the “double-edge sword” with cell-mediated response?
You get both immunity and hypersensitivity
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?
Lepromatous:
- *Antibody:** yes
- *DTH:** no
- *Acid fast:** yes
- *granuloma:** no
- *Type of T-cell:** Th2
- *IL-12:** no
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?
_Tuberculoid _
- *Antibody:** no
- *DTH:** yes
- *Acid fast:** no
- *granuloma:** yes
- *Type of T-cell:** Th1
- *IL-12:** yes
What is the “master switch” that determined whether or not you get an antibody response?
IL-12
- secreted by macrophages
- induces Th to differentiate into Th1
- if naive Th doesn’t get signal, it will become Th2
What is an iNKT cell? Where do you usually see them?
- invariant natural killer cell
- natural, innate immunity, not adaptive immune response
- reacts with lipid antigens
- found in patients with asthma and ulcerative colitis
What are the two subsets of Type IV sensitivity?
- Cytokine-driven or “classical”
- Cytotoxic Lymphocytes
List the main players in Cyotkine-driven Type IV hypersensitivity and their actions
-
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
Classic example of Cyotkine-driven Type IV hypersensitivity
Tuberculosis
What is secondary TB and its cause?
- 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
List the main players in Cytotoxic T-lymphocyte (CTL) subset of Type IV hypersensitivity
- 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.
What makes CTL-1 (cytotoxic T lymphocyte) unique?
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+ !
Why have a CD4+ killer cell?
- macrophages have MHC II which CANNOT be recognized by CD8+
- CD4+ killer cell can recognize it and kill it
What is the main cause of rapid replication of keratinocytes in Psoriasis?
Th 22 cells –> IL-22 –> cell replication stimulation –> target keratinocytes, induce proliferation, anti-apoptotic pathways, acanthosis, and parakeratosis
IL-17
- Th17 CD4+ cells make it
- suddenly appear in some patients with psoriasis and induce acute inflammatory repsonse
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
Clinical presentation
Major player
- 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
What are the two necessary signals for activation of Cytotoxic T cells?
- Pre-cytotoxic T cell CD8+ recognizes antigen on MHC I
- 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
