Chapter 6: Diseases of the Immune System Part 1 Flashcards
1
Q
What are the major components and cells of the innate immunity?
A
- Epithelial barriers
- Phagocytic cells (neutrophils and macrophages)
- DCs
- NK cells
- Complement proteins
2
Q
How is complement system activated in innate vs. adaptive immune response?
A
Innate: microbes using the alternative and lectin pathways
Adaptive: by antibodies using the classical pathway (GM makes classic cars)
3
Q
Which cells involved in the initiation of the innate immune response?
A
Dendritic cells
4
Q
Function of mannose-binding lectin and C-reactive protein in the innate immune response?
A
Coat microbes and promote phagocytosis
5
Q
What are examples of plasma proteins in the innate immune response?
A
- Complement
- Mannose-binding lectin and CRP
- Lung surfactant
6
Q
What cells provide early protection against viruses and intracellular bacteria?
A
Nk cells
7
Q
What are the plasma membrane PRRs used to detect extraceullar microbes?
What does each detect?
A
- TLR = bacterial products
- C-type Lectin receptor (CLRs) = microbial polysaccharides
8
Q
TLRs present in the plasma membrane and endosomal vesicles signal via a common pathway that leads to activation of what 2 sets of transcription factors?
A
1) NF-kB, stimulates synthesis and secretion of cytokines and expression of adhesion molecules, both critical for recruitment and activation of leukocytes
2) Interferon regulatory factors (IRFs), which stimulate production of antiviral cytokines, type I interferons
9
Q
Where are NOD-like receptors found and what do they recognize?
A
- Cytosolic receptors
- Recognize products of necrotic cells like uric acid, ATP, ion disturbances (i.e., loss of K+), and some microbial products
10
Q
Several NOD-like receptors (NLRs) signal via which cytosolic multiprotein complex, which activates?
Gain of functon mutations in one of NLRs results in?
How are these mutations treated?
A
- NLRP3 (sensor) of Inflammasomewhich activatescaspase-1that cleavespro-IL-1β to its active form.IL-1β involved in recruitment of leukocytes and induction offeverduringacute inflammatory process
- Gain-of-function mutations result in periodic fever syndromes, called autoinflammatory syndromes
- Respond well to IL-1 antagonists
11
Q
NLR-inflammasome pathway may play a role in what disorders?
A
- Recognition of urate crystals by class of NLRs underlies inflammation in Gout
- Obesity-associated type 2 diabetes (recognition of lipids deposited in tissues)
- Atherosclerosis (recognition of cholesterol crystals)
12
Q
C-type lectin receptors are expressed where?
Detect what?
A
- Plasma membrane of macrophages and DCs
- Detect fungal glycan and elicit inflammatory rxns to fungi
13
Q
RIG-like receptors are located where and detect what?
Stimulate production of?
A
- Located in cytosol
- Detect nucleic acids of viruses that replicate in the cytoplasm
- Stimulate production of antiviral cytokines
14
Q
GPCRs located on what immune cells and recognize?
A
- Neutrophils, macrophages, and most other types of leukocytes
- Recognize short bacterial peptides containing N-fMet
15
Q
Somatic recombination which generates Lymphocyte diversity in both the thymus and bone marrow is mediated by what enzyme/genes?
Mutation of these genes results in?
A
- Enzyme product of RAG-1 and RAG-2 (recombinant activating genes)
- Failure to generate mature lymphocytes
16
Q
What are the recombined (aka rearranged) antigen receptors found on B and T cells?
A
B cell = Ig
T cells = TCR
17
Q
How is analysis of antigen receptor gene rearrangements a valuable assay for detecting lymphomas?
How is this done?
A
- Moleulcar assays using PCR can determine if a lymphocyte proliferation is polyclonal (non-neoplastic)ormonoclonal (neoplastic)
- Each T or B cell and its clonal progeny have a unique DNA rearrangement (and hence unique antigen receptor)
18
Q
95% of the TCRs are heterodimers consisting of what kind of chain?
Recognize Ags how?
A
- Consist of α and β polypeptide chains
- Recognize Ags presented by MHCs on surface of APCs
19
Q
Small population of mature T cells contain a γδ TCRs which recognizes?
Tend to aggregate where?
A
- Recognize peptides, lipids, and small molecules WITHOUT assistance from MHC proteins
- Aggregate at epithelial surfaces, such as the skin and mucosa of GI and Urogenital tract
20
Q
NK-T cells recognize what?
A
Glycolipids displayed by MHC-like molecule CD1
21
Q
Cytokine-secreting helper cell that assists macrophages and B lymphocytes to combat infections describes what cell type?
A
CD4+ T cells
22
Q
Which Ig’s present on the surface of all mature, naive B cells are the antigen-binding component of the B-cell receptor complex?
A
IgM and IgD
23
Q
What heterodimer of invariant proteins is found on the B-cell antigen receptor and are essential for signal transduction?
What are other important molecules are expressed on B cells that are essential for their responses?
A
- Igα (CD79a) and Igβ (CD79b) essential for signal transduction
- Type 2 complement receptor (CR2 or CD21) recognizes complement products generated during innate response
- CD40 receives signals from helper T cells
24
Q
Epstein-Barr virus (EBV) can use which receptor to enter and infect B cells?
A
CR2 (type 2 complement receptor)
25
Where are follicular DCs found?
What kind of receptors do they have, which allows them to do what?
Play a role in which immune response and how?
- Germinal centers of lymphoid follicles in **spleen** and **LNs**
- Have **Fc receptors** for **IgG** and **receptors for C3b =** can trap Ag bound to Ab's or complement proteins
- Play role in **humoral** immune response by presenting Ags to B cells and selecting B cells that have the **highest affinity** = improving quality of antibody produced
26
What are 3 important functions of macrophages?
1. Function as APCs in T-cell activation
2. Key effector cells in certain forms of cell-mediated immunity. T cells activate macrophages and enhance their ability to kill ingested microbes
3. Participate in effector phase of humoral immunity, by efficient phagocytosis and destruction of opsonized (coated) microbes by IgG or C3b
27
NK cells contain abundant?
What 2 cell surface molecules are commonly used to identify NK cells?
- Abundant **azurophilic granules**
- CD16 and CD56
28
Which cells function to destroy irreversibly stressed and abnormal cells, such as virus-infected and tumor cells?
Natural Killer (NK) Cells
29
Function of CD16 found of NK cells?
An **Fc** receptor for **IgG**, confers the ability for NK cells to lyse IgG-coated target cells, known as **antibody-dependent** **cell-mediated cytotoxicity (ADCC)**
30
How are NK cells able to recognize and kill infected cells?
- Contain an **activating** receptor **NKG2D** which recognizes surface molecules induced by various kinds of stress, such as infection and DNA damage
- Contain an **inhibitory** receptor, which recognizes **MHC class** I molecules, that are expressed by all healthy cells
- When cell is infected, expression of ligands for the activating receptor will be enhanced, while expression of MHC class I molecules are reduced, balance is tilted towards activation/killing by NK cell.
31
What cytokine do NK cells secrete; function?
IFN-gamma
Activates macrophages to destroy ingested microbes, thus NK cells provide early defense against intracellular microbial infections
32
Which cytokines regulate NK cells?
How does each have an effect?
- **IL-2** and **IL-15** stimulate **proliferation** of NK cells
- **IL-12** activates **killing** and **secretion** of **IFN-gamma** by NK cells; IFN-gamma then activates Macrophages (classical) to destroy
33
MHC molecules are called what?
Encoded where?
- Human leukocyte antigens (**HLA**)
- Chromosome **6**
34
MHC class I molecules are expressed on what cells?
The α/heavy chain is encoded by what 3 genes?
Display what antigens?
- All **nucleated cells** and **platelets**
- HLA-A, HLA-B, HLA-C
- Peptides derived from proteins, such as viral and tumor Ags located in the cytoplasm (**intracellular**)
35
Function of α1, α2, and α3 extracellular domains of the α/heavy-chain of MHC class I?
- **α1** and **α2** form a **cleft**, or **groove**, where peptides bind
- **α3** is nonpolymorphic and has binding site for **CD8**
36
MHC class II molecules mainly expressed on what cells?
Encoded in which region and subregions?
Display what Ags?
- Macrophages, B cells, and DCs = ALL **APCs**
- Encoded by **HLA-D region**, which has 3 subregions: **HLA-DP, HLA-DQ, and HLA-DR**
- Display Ags that are internalized into vesicles and typically derived from **extracellular** microbes and **soluble proteins**
37
What makes up the peptide binding cleft of the MHC class II molecule?
What portion of MHC class II has binding site for CD4?
- **α1** and **β1** domains interact and form cleft = **binding groove**
- **β2** domain has binding site for CD4
38
Peptide-loaded MHC class I molecules associate with _______ to form a stable trimer that is transported to the cell surface?
**β2-microglobulin**
39
How are HLA genes inherited?
Why are there virtually innumerable combos of HLA molecules?
- One set of HLA genes from each parent
- Polymorphisms cause each individual to express an MHC profile on his or her cell surface that is different from the halotypes of most other individuals
40
What role do MHC molecules play in regulating T cell-mediated immune responses?
- Determines if an immune response against a specific Ag will occur protein, since you must inherit the genes for those MHC molcules that can bind the specific Ag and present it to T cells (i.e., ragweed pollen)
- Ensure the correct immune response is mounted against different microbes, i.e., CTL-mediated killing of cells and helper T cell-mediated Ab and macrophage activation for extracellular microbes
41
Which cytokines stimulate hematopoiesis?
GM-CSF and IL-7
42
Patients w/ Rheumatoid arthritis respond dramatically to which type of treatment?
TNF antagonists
43
What is an example of therapeutically administering cytokines to boost reactions?
To mobilize and recruit stem cells from bone marrow to peripheral blood; the cells are then collected from the blood for **stem cell transplantation**
44
The spleen serves the same role in immune responses to ______ antigen as LN do in response to \_\_\_\_\_\_\_?
The spleen serves the same role in immune responses to **blood borne** antigen as LN do in response to **lymph-borne antigens**
45
How are antigens trapped in the spleen?
DCs and macrophages
46
Where are cutaneous and mucosal lymphoid systems located?
How many lymphocytes found here?
Function of these systems?
- Under the epithelia of the skin, GI, and respiratory tracts
- 1/2 of body's lymphocytes are in the mucosal tissues
- Respond to Ag's that enter through breaches in the epithelium
47
Where in the spleen do the T lymphocytes and B cells reside?
- T lymphocytes concentrated in **periarteriolar lymphoid sheaths**
- B cells reside in the **follicles**
48
In the case of immunization with a protein antigen, microbial mimics, called _______ are given w/ the antigen and these stimulate the innate immune response
Adjuvants
49
What are the principal costimulators for T cells and what are they recognized by on the naive T cell?
- B7 proteins (CD80 and CD86)
- Recognized by CD28 receptor on naive T cells
50
One of the earliest responses of CD4+ helper T cells is the secretion of what important cytokine and expression of what receptor?
Function of this cytokine?
- Secretion of IL-2 and expression of **high-affinity** IL-2R
- IL-2 is a **growth factor** that acts on T lymphocytes and **stimulates proliferation**
51
When CD4+ helper T cells recognize Ag's displayed by macrophages or B lymphocytes, which ligand and co-receptor are expressed?
T cells express **CD40L**, which engages CD40 on the macrophages or B cells and **activates** these cells
52
Major cytokines produced by TH2 cells?
Which cytokine induces TH2 cells?
- IL-4, IL-5, IL-13
- Induced by IL-4
53
The cytokines IL-4 and IL-5 produced by TH2 cells play what important roles?
- IL-4 ---\> **IgE** class switching
- IL-5 ---\> **IgA** class switching; activates **eosinophils**
54
What binds to IgE-coated helminthic parasites, and functions to eliminate helminths?
Eosinophils and Mast cells
55
Which cells play a role in autoimmune disease and chronic inflammatory disease (such as IBD, psoriasis, and granulomatous inflammation)?
TH1 cells
56
Which cells play a role in autoimmune and other chronic inflammatory diseases (such as IBD, psoriasis, and MS)?
TH17 cells
57
Which cells induce TH17 cells?
What do TH17 cells produce?
- **Induced** by TGF-β, IL-6, IL-1, and IL-23
- **Secrete** IL-17 and IL-22
58
Which cells provide host defense against extracellular bacteria and fungi?
TH17 by recruiting neutrophils and monocytes
59
What cells and cell surface molecule plays key roles in the ability of protein antigens to induce the production of antibodies of different classes or isotypes such as IgG, IgA, and IgE?
Cytokines which induce isotype switching?
- CD40L and helper T-cell actions (**T-cell dependent**)
- Isotype switching induced by cytokines **IFN-gamma** and **IL-4**
- Helper T cells stimulate the production of Abs with **high affinities** for the **antigen**
60
What are T-independent responses?
What does this type of response lack?
Main Ig involved?
- Many polysaccharide and lipid Ags **cannot** be recognized by T cells but have multiple identical antigenic determinants (**epitopes**) that are able to engage many antigen receptor molecules on each B cells and initiate B cell activation
- **No immunoglobulin isotype switching** and **affinity maturation** (requires T cells)
- Mainly **IgM**
61
Where is IgA found most abundantly?
Mucosal epithelia such as in lumen of respiratory and GI tract (and other mucosal tissues)
62
Which antibody may be transported across the placenta and provides immunuity for the newborn?
IgG
63
\_\_\_\_\_ and _____ cooperate to kill parasites such as helminths (worms)
Mainly by?
**IgE** and **eosinophils**; mainly by release of eosinophil granule contents that are toxic to worms
64
What characterizes the immediate reaction of type I hypersensitivity?
Cell type involved?
Length of time?
- Vasodilation, vascular leakage/edema, smooth muscle spasm, granular secretions
- Antigen binds to IgE on the surface of mast cells = **allergy** caused by an **allergen**
- **Minutes to hours**
65
What characterizes the late-phase reaction in type I hypersensitivity?
Length of time?
Dominant cell types?
- 2-24 hours after exposure **without** additional exposure
- Last several days
- Infiltration of tissues w/ **eosinophils, neutrophils, basophils, monocytes, CD4+ T cell**
66
Most immediate hypersensitivity disorders are caused by excessive _______ responses and these cells play a central role by stimulating ______ production and promoting inflammation
Most immediate hypersensitivity disorders are caused by excessive **TH2** responses and these cells play a central role by stimulating **IgE** production and promoting inflammation
67
Role of IL-13 secreted by TH2 cells in immediate (type I) hypersensitivity?
Enhances IgE production and acts on epithelial cells to **stimulate mucus secretion**
68
What are similarities and differences between mast cells and basophils?
- **Both** have presence of IgE Fc receptors and cytoplasmic granules
- **Basophils** are not normally present in tissues but rather **circulate in the blood**
- **Mast cells** are widely distributed in **tissues**, abundant near BV's and nerves
69
What found inside Mast cells helps us to visualize them histologically?
Acidic proteoglycans which bind basic dyes such as **touidine blue**
70
What can trigger mast cells?
- Cross-linking IgE Fc receptors
- C5a and C3a
- IL-8
- Codeine and morphine (make you itch)
- Adenosine
- Melittin (bee venom)
- Physical stimuli (i.e., heat, cold, sunlight)
71
Explain the sequence of events in an type I hypersensitivity reaction starting with the introduction of an allergen
- Naive CD4+ T-cells activated by a DC presenting an Ag; IL-4 cause T cells to differentiate into TH2 cells, which then produce IL-4, IL-5, and IL-13
- IL-4 acts on B cells, promoting class switching to IgE and development of more TH2 cells
- IL-5 activates eosinophils
- IL-13 enhances IgE production and acts on epithelial cells to stimulate mucus secretion
- IgE produced by plasma cells binds to Mast cell FcERI receptor and "**sensitizes"** it
72
What are the most potent vasoactive and spasmogenic agents known?
LTC4 and LTD4
73
What is the most abundant mediator produced in mast cells by the cyclooxygenase pathway, which causes intense bronchospasm as well as increased mucus secretion?
Prostaglandin D2
74
What substance released by some mast cells causes platelet aggregation, release of histamine, bronchospasm, increased vascular permeability, and vasodilation?
Platelet-activating factor (PAF)
75
Which cytokines released by Mast cells and their functions?
- **TNF, IL-1, chemokines**: promote leukocyte recruitment (typical of **late-phase** reaction)
- **IL-4**: which amplifies the TH2 response
76
During the late-phase reaction of a type I hypersensitivity what do eosinophils cause?
What do they release?
- Damage tissues via release of:
- Proeolytic enzymes
- **Major basic protein**
- Eosinophil cationic protein
77
Late-phase reaction is a major cause of symptoms in some type I hypersensitivity disorders such as?
What is used to treat these?
- Allergic asthma
- Tx with **broad-spectrum anti-inflammatory** drugs, such as **steroids**
- Anti-histamine drugs are **only useful** for the **immediate reaction**
78
What molecule is chemotactic for eosinophils?
Eotaxin
79
Increased propensity to develop immediate hypersensitivity reaction is called what?
These pt's have higher levels of?
- Atopy
- Higher levels of serum **IgE**, more **IL-4** producing TH2
80
Studies in patients with asthma reveal linkage to polymorphisms in genes encoding the cytokines IL-3, IL-4, IL-5, IL-9, IL-13, and GM-CSF, which are **found on what chromosome?**
Also noted to which chromosome close to the HLA complex?
- **5**q31 (chromosome **5**)
- 6p (chromosome **6**)
81
What commonly triggers bronchial asthma?
Viral infections of the airways
82
What is a Non-atopic allergy?
- Triggered by non-antigenic stimuli: **temperature extremes and exercise**
- Does **NOT** involve **TH2 cells** or **IgE**
- Thought to be mast cells that are abnormally sensitive to acitvation by nonimmune stimuli
83
What are 4 clinical syndromes that are a result of immediate hypersensitivity reactions?
1) Anaphylaxis (may be from drugs, bee sting, food)
2) Bronchial asthma
3) Allergic rhinitis
4) Food allergies
84
Systemic Anaphylaxis is characterized by?
What is the immediate response and is then followed by?
- Vascular shock, widespread edema, and difficulty in breathing
- **Within minutes**: itching, hives, and skin erythema
- **Followed by:** striking contraction of bronchioles and respiratory distress
- Laryngeal edema --\> hoarsness and further compromises breathing
- Vomiting, diarrhea, abdominal cramps, and laryngeal obstruction follow
85
Antibody-mediated (type II) hypersensitivity involve what specific antibodies and can target what antigens?
- IgG and IgM
- Can be **autoantibodies**: specific for normal cell or tissue Ags
- Antibodies to **exogenous Ags**, such as chemical or microbial proteins
86
In type II hypersensitivities what are the mechanisms for which antibodies destroy cells?
- **Opsonization and phagocytosis:** cells opsonized by IgG recognized by phagocyte Fc receptors; IgG and IgM on cell surfaces may also activate classical pathway
- **Antibody-dependent cellular cytotoxicity (ADCC)**: cells coated with IgG are killed by variety of effector cells, mainly NK and macrophages; cell lysis **W/O** phagocytosis
87
Complement activation can lead to the formation of the MAC, which disrupts membrane integrity of cells by "drilling holes," which cells is the MOA most effective against?
Cells that have **thin walls** ---\> *Neisseria* bacteria
88
Clinically antibody-mediated cell destruction and phagocytosis occur in what 4 situations?
1) **Transfusion rxns**: cells from incompatible donor react with and are **opsonized** by **preformed Ab** in host
2) **Hemolytic disease of newborn (erythroblastosis fetalis)**: antigenic difference between mom and baby; IgG antierythrocyte Abs from mom cross placenta and destroy fetal red cells
3) **Autoimmine hemolytic anemia, agranulocytosis,** and **thrombocytopenia**: pt makes Abs to their own blood cells
4) **Certain drug rxns:** drug acts as a **"hapten"** by attaching to plasma membrane proteins of red cells and Abs are produced against the drug-protein complex
89
What is the mechanism responsible for tissue injury in some forms of Glomerulonephritis and vascular rejection in organ grafts among others?
Antibody-mediated inflammation
90
Pink-colored urine after a blood transfusion indicates?
Hemolysis of RBCs occuring due to antibody mediated activation of complement
91
How do deposited antibodies in fixed tissues, such as basement membranes and ECM cause injury due to inflammation?
1) Activate complement, generating by-products, including **chemotactic agents (C5a)**, which brings polymorphonuclear leukocytes and monocytes to tisse
2) Activate **anaphylatoxins (C3a and C5a)**, which **increase vascular permeability**
92
What do antibodies do in Myathenia gravis?
React with **ACh receptors** in the motor end plates of skeletal muscles and block (act as **antagonists**) neuromuscular transmission --\> muscle weakness
93
What do antibodies do in Graves disease?
Act as **agonists** on the TSH receptor of thyroid epithelial cells and stimulate the cells to make thyroid hormones ---\> **hyperthyroidism**
94
Pemphigus vulgaris, Goodpasture syndrome, Acute rheumatic fever, Insulin-resistant diabetes, and pernicious anemia are examples of what type of hyerpsensitivity?
Type II Hypersensitivity
95
Type III Hypersensitivity preferentially involve what 3 organs/sites?
- Kidney (glomerulonephritis)
- Joints (arthritis)
- Small blood vessels (vasculitis)
\*Organs where blood is filtered at **high pressure** to form other fluids, like urine and synovial fluid.
96
What is the basis of an immune complex-mediated (type III) hypersensitivity reaction?
What type of antigens involved?
- IgM and IgM antibodies bind antigens usually in circulation and the antigen-antibody complex deposits in vessel walls and induce inflammation (vasculitis)
- Antigens can be **exogenous** and **endogenous**
97
List 6 scenarios/diseases that involve immune-complex mediated (type III) hypersensitivity?
1) Systemic lupus erythematous
2) Poststreptococcal glomerulonephritis
3) Polyarteritis nodosa
4) Reactive arthritis
5) Serum sickness
6) Arthus reaction (experimental)
98
What is the prototype of a systemic immune complex disease?
Explain this process and what its used for?
- Acute serum sickness
- Someone is given anti-serum derived from another species, such as serum from immunized horses (against diptheria) or rattlesnake antidote
- Antidote will neutralize the toxin you were exposed to, but at same time your body will attack the antiserum forming immune complexes and causing symptoms of serum sickness
99
What can be used to monitor disease activity of Type III Hypersensitivity?
- Complement proteins can be detected at site of injury, and during active phase of disease consumption of complement will lead to decrease in serum C3
- Serum levels of C3 can be used to monitor the disease activity
100
Briefly describe the 3 phases of the pathogenesis of systemic immune complex disease (main players and time line of events).
1. **Formation of immune complex**: intro of protein Ags triggers immune response resulting in formation of Abs, typically 7 days after injection of the protein. Secreted into blood where they react with Ag still present and form complexes
2. **Deposition of complex:** Ag-Ab complex (medium sized/slight Ag excess = most pathogenic) deposit in tissues/organs
3. **Inflammation/tissue injury:** acute inflammatory rxn, about 10 days after Ag was introduced producing fever, urticaria, arthralgia, lymphadenopathy, and proteinuria
101
What occurs in the Arthus reaction?
How can it be produced experimentally and what is the end result?
- Localized area of tissue necrosis resulting from acute immune complex vasculitis, usually elicited in skin
- Experimentally by intracutaneous injection of Ag in a previously immunized animal that contains circulating Abs against the Ag.
- As Ag diffuses into the vascular wall, binds preformed Ab and large immune complexes are formed **locally.** Precipitate in vessel walls and cause **fibrinoid necrosis**
102
What induces the pathologic lesions of immune complex disorders?
Complement-fixing Abs (IgG and IgM) and Abs that bind to leukocyte Fc receptors
103
What causes type IV hypersensitivity?
Inflammation resulting from cytokines produced by CD4+ T cells and killing by CD8+ T cells
104
What do Th17 cells produce which will amplify the TH17 response?
IL-21
105
What are 6 examples of T-cell mediated (type IV) hypersensitvity diseases?
1. Rheumatoid arthritis
2. Multiple Sclerosis
3. Type I DM
4. Inflammatory bowel disease
5. Psoriasis
6. Contact sensitivity
106
What is the classic example of a Delayed Type Hypersensivity?
How does this work?
- Tuberculin reaction
- Purified protein derivative (PPD; aka tuberculin), a protein-containing Ag of the tubercle bacillus is injected intracutaneously.
- Previously sensitized pt's will have reddening and induration of the site appear in 8-12 hrs and peaking at 24-72 hrs
107
What are the epithelial barriers of innate immunity?
What can it produce?
- Skin, GI, and respiratory tracts
- Antimicrobials (defensins)
108
If APC's produce IL-12 which T helper cell will CD4+ T cells differentiate into?
How about if they produce IL-1, IL-6, and IL-23?
- IL-12 ---\> TH1 ---\> IFN-gamma ---\> more TH1
- IL-1, IL-6, IL-23 ---\> TH17
109
Inflammation produced in psoriasis is mediated mainly by cytokines produced by?
What type of hypersensitivity is this?
- TH17
- T-cell mediated (Type IV) hypersensitivity
110
Activated TH17 cells produce which cytokines and how do they contribute to the inflammatory response of typer IV hypersensitivities?
- IL-17, IL-21, IL-22, and chemokines
- Collectively, recruit **neutrophils** and monocytes to the rxn, thus promoting inflammation
- IL-21 **amplifies** the TH17 response
111
What is the predominate infiltrate in the lungs after 2-3 weeks of a tuberculous infection?
Sustained activation causes these cells to undergo?
- Macrophages
- Undergo **morphologic** transformation into **epitheloid cells**, which will be surrounded by collar of lymphocytes, and referred to as a **granuloma**
112
Granulomatous inflammation is associated with strong _____ activation and high-level of cytokines such as \_\_\_\_\_.
Granulomatous inflammation is associated with strong **TH1-cell** activation and high-level of cytokines such as **IFN-gamma**
113
Contact dermatitis is tissue injury resulting from what type of reaction?
How do these substances cause a rxn?
- Delayed-Type Hypersensitivity (IV)
- Enviornmental chemical (i.e., urushiol from poison ivy, nickel) binds to and structurally modifies a self-protein, and peptides from this self-protein ("neoantigens") are then recognized by T cells as foreign
114
The tissue injury in type I diabetes, **graft rejection**, reactions against viruses, and killing tumor cells is mediated by what type of T cell response?
CD8+ T cell-Mediated Cytotoxicity
115
Gut Microbiome plays important role in?
**- Local** and **Systemic** immune functions\
- Brain development
- Metabolic functions
- Hormones and neurochemical production
- Provide biofilm protection
116
The gut microbiome of a child is similar to that of an adult by what age?
3-4 years
117
Dysbiosis is implicated in which diseases?
IBD
Allergy
Autoimmune diseases
