Cells of Immunity Flashcards
NK natural killer cells are a member of which type of immunity?
Innate immunity
NK natural killer cells target which type of cells?
Virally infected cells
Tumor cells
What mechanisms do NK natural killer cells use to induce apoptosis?
Perforin
Granzymes
NK natural killer cells activity is increased in the presence of which cytokines?
IL-2
IL-12
IFN-α
IFN-β
CD16 & CD56 can clinically enumerate which type of cells?
NK natural killer cells
CD16: Opsonization ADCC
CD56: Cell adhesion
How are NK natural killer cells activated?
When exposed to nonspecific activation signal on target cell
and/or
An absence of MHC I on target cell surface
and/or
ADCC antibody-dependent cell-mediated cytotoxicity (CD16 binds Fc region of bound Ig → activating NK cells)
Perforins & granzymes are part of which lymphocytes mechanism for killing?
NK natural killer cells
B cells are a member of which type of immunity?
Humoral immunity (adaptive)
T cells mediate which type of immunity?
Cell-mediated immunity (adaptive)
Recognizing antigen and undergoing somatic hypermutation to optimize antigen specificity is a function of which cells?
B cells
What are major function of B cells?
Recognize Ag
- undergo somatic hypermutation to optimize Ag specificity
Produce Antibodies
- differentiate into plasma cells to secrete specific Igs
Maintain immunologic memory
- memory B cells persist & accelerate future response to Ag
T cells are a part of which type of hypersensitivity?
Delayed cell-mediated hypersensitivity (type IV)
What are major function of T cells?
CD4+ T cells
- help B cells make antibodies
- produce cytokines to recruit phagocytes
- activate other leukocytes
CD8+ T cells
- directly kill virus-infected cells
- kill neoplastic cells
- kill donor graft cells (apoptosis)
Where does the positive selection of T cells take place?
Thymic cortex
Where does the negative selection of T cells take place?
Thymic medulla
Which cells are the APC (antigen presenting cells)?
B cells
Dendritic cells
Macrophages
Langerhans cells
What is T cell positive selection?
T cells expressing TCRs capable of binding self-MHC with low affinity on cortical epithelial cells → survive & mature
What is failure of positive selection?
T cells that fail to recognize self-MHC (self-antigen) at all will not survive & mature
What is T cell negative selection?
T cells that bind too strongly (high affinity) to self-MHC and self-peptide undergo apoptosis
(b/c these cells have potential to cause autoimmune disease)
What is the function of AIRE (autoimmune regulator)?
Tissue-restricted self-antigens are expressed in thymus & enhances clonal deletion of auto-reactive thymocytes
(It exposes T cells to normal, healthy proteins from all parts of the body, and T cells cannot bind Ag without MHC but it makes them do it anyway and if they react to those proteins, they are destroyed)
What AIRE (autoimmune regulator) deficiency lead to?
APS1
Autoimmune polyendocrinopathy syndrome type 1
APECED
Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy
CD4+ cells that recognize MHC II will eventually mature into which cells?
Helper T cells (Th)
CD8+ cells that recognize MHC I will eventually mature into which cells?
Cytotoxic T Lymphocytes (CTLs)
Helper T cells are the CD4+ cells which recognize which class of MHC?
MHC II
Cytotoxic T lymphocytes are CD8+ cells which recognize which MHC class?
MHC I
What are the effector mechanisms controlled by Th cells?
Antibody synthesis
Macrophage activation
CTL killing
What is CD4+ T cell first signal?
Recognition of specific antigen complexed to
dendritic cell) MHC II ↔ TCR (CD4+ Th cell
What is CD4+ costimulatory signal?
Co-stimulation through binding of
B7 (APC) ↔ CD28
What is the pattern of differentiation of helper T cells is determined by?
Antigen (type of pathogen causing infection)
Cytokines (produced in response to antigen)
Transcription factors (stimulated by cytokines)
Th1 cells secrete which cytokines?
IFN-γ
IL-2
Differentiation of Th1 cells is induced by which cytokines?
IFN-γ
IL-12
Th1 cells are inhibited by which cytokines?
IL-4
IL-10
IL-13
(from Th2 cells)
IL-4 & IL-10 inhibit which type of cells?
Th1 cells
IFN-γ & IL-12 cause differentiation if which cells?
Th1 cells
Th2 cells secrete which cytokines?
IL-4
IL-5
IL-6
IL-10
IL-13
Differentiation of Th2 cells is induced by which cytokines?
IL-2
IL-4
Th2 cells are inhibited by which cytokines?
IFN-γ
from Th1 cell
Intracellular infections promote differentiation of which type of cells?
Th1 cells
Functions of Th1 cells
Activate macrophages & cytotoxic T cells
Intracellular infection response
(transcription factor T-bet) → secrete
IFN-γ
- ↑Th1 response
- ↓Th2 response
- activate classical macrophage
- isotype switching to IgG
&
IL-2
- ↑ proliferation & activity of Ag-primed Th & CTLs
Functions of Th2 cells
Parasitic infection response (transcription factor GATA3) → activate eosinophils, IgE
IL-4
- ↑Th2 response
IL-4 & IL-13
- Isotype switching to IgE
- activate alternative macrophage
IL-5
- Eosinophil activation & maturation
TGF-β
- Isotype switching to IgA
IL-4 & IL-10
- ↓Th2 response
Functions of Th17 cells
Induce neutrophilic inflammation
-Extracellular bacterial & fungal infection response (transcription factor RORγT) → secrete
- IL-17
- activates tissue cells & leukocytes to secrete inflammatory cytokines → recruitment of neutrophils
- IL-17/ IL-21/ IL-22
- act on epithelial cells to secrete antimicrobials
- improve endothelial barrier function
Functions of Th reg cell
Maintain tolerance/ regulate (inhibit) Th1 function (transcription factor FoxP3 & CD3, CD4, CD25) & prevent autoimmunity
IL-10/ IL-35/ TGF-β
- anti-inflammatory
- ↓CD4
- ↓CD8
What is IPEX syndrome?
Immune dysregulation
Polyendocrinopathy
Enteropathy
X-linked syndrome
Genetic deficiency FoxP3 → autoimmunity
- enteropathy
- endocrinopathy
- nail dystrophy
- dermatitis
- derma issues
- associated with DM in male infants
Deficiency of FoxP3 causes which disorder?
IPEX syndrome
Immune dysregulation
Polyendocrinopathy
Enteropathy
X-linked syndrome
What is antigen presentation?
Needed for T cell activation
Dendritic cell (specialized APC) sample antigen → process antigen → migrate to draining lymph node to look for naïve T lymphocyte to present antigen
What signals are required for T cell activation?
Primary T cell activation involves the integration of three distinct signals after antigen recognition:
(1) T-cell activation (first signal)
MHC II ↔ TCR on CD4
or
MHC I ↔ CD8+ T cytotoxic cells
(2) Proliferation & survival (costimulatory signal)
APC (CD80/86) B7 ↔ CD28 (naive T cell)
(3) Differentiation (cytokine- mediated)
T helper cell activate & produce
IL-4/ IL-6/ IL-12/ TGF-β
T cytotoxic cells activate & kill virus-infected cell
What is the first signal for T cell activation?
Recognition of specific antigen complexed to
(dendritic cell) MHC II ↔ TCR (CD4+ Th cell)
or
endogenous or cross-presented antigen is presented on
MHC I ↔ CD8+ T cytotoxic cells
What is anergy?
Anergy is a state during which a cell cannot become activated by exposure to its antigen.
T and B cells become anergic when exposed to their antigen without costimulatory signal
[failure of signal 2:
APC (CD80/86) B7 ↔ CD28 (naive T cell)]
Another mechanism of self-tolerance.
Steps in B cells activation
First signal
- mature naïve B lymphocytes circulating and aggregating in follicular areas of 2° lymphoid organs (lymph nodes & spleen)
- antigen bind and cross-link idiotype of the immunoglobulin
Thymus independent B cell activation
TI-Antigen activated B cells
- Thymus independent
- Macromolecules (lipids, polysaccharides, lipopolysaccharides) (gram -ive bacteria) lack peptide component
- directly stimulate B cell (don’t require T helper cell)
- weaker response than TD (weak immunogenic)
- IgM mostly
- no memory
-vaccines often require boosters & adjuvants (pneumococcal polysaccharide vaccine)
Thymus dependent B cell activation
TD-Antigen activated B cells
- thymus dependent
- contain protein component (diptheria vaccine)
(1) T helper cell activation (1st/2nd/3rd signals)
(2) B cell receptor-mediated endocytosis
(3) antigen presented on MHC II ↔ TCR (T helper cells)
(4) B cell CD40 ↔ CD40L ligand (T helper cell)
(5) T helper cell secrete cytokines → Ig class switching of B cell → B cell activates → class switching → affinity maturation → antibody maturation
CD40 ↔ CD40L ligand binding is part of which cell activation?
B cell activation (thymus (T helper cell) dependent)
What is co-stimulatory signal of primary T cell activation?
Why is it necessary?
APC (CD80/86) B7 ↔ CD28 (naive T cell)
Proliferation & survival
Which cells determine Ig class isotype switching?
T helper cells
What is the principal immunoglobulin of the primary immune response when antigen is first encountered?
IgM
IL-4 & IL-13 induce class switching to which Ig?
IgE
IL-5 & TGF-β induce class switching to which Ig?
IgA
The process in which T cells that bind too strongly (high affinity) to self-MHC and self-peptide undergo apoptosis or become regulatory T cells is called?
Negative selection
APS1 Autoimmune polyendocrinopathy syndrome type 1 features?
CHAR
Chronic mucocutaneous candidiasis
Hypoparathyroidism
Adrenal insufficiency
Recurrent Candida infections
Autoimmune polyendocrine syndrome-1 is a failure of which part of T cell differentiation?
Negative selection
Tissue-restricted self-antigens are expressed in the thymus due to autoimmune regulator (AIRE)
so T cells expressing TCRs with high affinity for self antigens will not undergo apoptosis
IL-10 & IL-35 & TGF-β are secreted by which T cells?
Function?
Th reg cell
- anti-inflammatory
- ↓CD4
- ↓CD8
Th17 secrete which cytokines?
IL-17
IL-21
IL-22
Treg cells secrete which cytokines?
TGF-β
IL-10
IL-35
Th17 cells are inhibited by which cytokines?
IFN-γ
IL-4
Treg cells are inhibited by which cytokines?
IL-6
IL-2 & IL-4 cause the differentiation & proliferation of which T cells?
Th2 cells
What happens if APC B7 does not bind to CD28 (on the naïve T cell) in presence of antigen?
What is this called?
No T cell activation (failure of costimulation signal)
Anergy
What is the adaptive immunity in which B lymphocytes produce antibodies?
Where are these antibodies present?
Humoral immunity
(humoral) circulate in blood as soluble protein
Which type of immunity is mediated by T cytotoxic and T helper cells?
Cell-mediated immunity
Which immunity is primary defense against extracellular pathogens and/or their toxins? Which cells provide it ?
Give some examples of extracellular threats?
Humoral immunity
(B cells)
Staphylococcus aureus
Streptococcus pyogenes
Pseudomonas aeruginosa
Escherichia coli
Which immunity is primary defense against intracellular microbes and tumors? Which cells provide it?
Some classical examples of intracellular pathogens?
Cell-mediated immunity
(T cells)
(viruses, bacteria, parasites, tumor cells)
Brucella abortus (brucellosis) Listeria monocytogenes (listeriosis) Chlamydia trachomatis Coxiella burnetii (Q fever) Mycobacterium tuberculosis Salmonella enterica
Immunity involving BCR receptors?
What are the accessory receptors in this type of immunity?
Humoral immunity
Igα & Igβ
(signal transducer protein complex by which Ig is attached to B cell)
CD40
CD21
Fc receptors
Immunity involving TCR receptors?
What are the accessory receptors in this type of immunity?
Cell-mediated immunity
CD2, CD3, CD4
CD8
CD28
Integrins
What molecules are responsible for transplant rejection?
MHC Class I and Class II molecules
On what types of cells are Class I MHC molecules expressed?
All nucleated cells
What are B cell receptors in their secreted, soluble form called?
Immunoglobulins (Ig) or antibodies
What components of an antibody bind antigen?
Fab region
Which type of immunity protects against cancers?
Cell-mediated immunity
Humoral immunity cannot eliminate tumor cells & transplants therefore cannot develop immunity
Which type of hypersensitivity can cell-mediated immunity cause?
Type IV hypersensitivity reaction (DTH)
A delayed-type hypersensitivity reaction to transplant is caused by which type of immunity response?
Cell-mediated immunity
