Immunology 1 Flashcards
The key regulatory cells are all T cells with which CD marker?
CD4+
Th17 cells produce which interleukin?
IL-17
Cytotoxic T cells have which CD marker?
CD8+
Allergic people and animals have a reduced number of which cells?
Allergen-specific Treg cells. This permits the inappropriate activation of allergen-specific Th2 cells and B cells and therefore the production of allergen-specific IgE antibody.
What are the four distinct levels of the skin barrier?
- The microbiome
- The chemical barrier
- The physical barrier
- The immunological barrier
Where are beta- defensins and cathelicidins derived from and what is their role in skin barrier function?
They are derived from keratinocytes and immune cells and may directly mediate microbial killing in addition to acting as leucocyte chemoattractants and immunomodulators.
What needs to be absent for a NK cell to recognise and destroy a target?
MHC Class I. The NK cell expresses an inhibitory receptor that binds to class I on normal tissue cells and prevents cytotoxicity from occurring.
What are:
PAMPs
MAMPs
DAMPs?
Pathogen associated molecular patterns
Micro-organism associated molecular patterns
Damage associated molecular patterns
What do PAMPs/MAMPs/DAMPs bind to on dendritic cells?
Pattern recognition receptors (Toll-like receptors)
What is T cell plasticity?
T cell lineage differentiation is not absolute and that it is possible for one type of mature effector to transform into another (e.g. Th1 to Treg) at a particular stage of an immune response.
Which cytokines do group 1 innate lymphoid cells produce and which cells to they stimulate/promote?
- Group 1 ILCs (ILC1 cells and NK cells) produce IFN-gamma and stimulate Th1 immunity
What modifications are made to the vascular endothelium at the site of antigen exposure?
- Transformation of vascular endothelial cells into larger cuboidal cells to increase turbulence and leukocyte-endothelial interaction
- Increased expression of E-selectin, ICAM-1, VCAM-1
Which cells do the below chemokines recruit?
IL-8 (CXCL8)
Monocyte chemotactic proteins
Eotaxins (CCL11, CCL24 and CCL26)
IL-8 (CXCL8) - neutrophils
Monocyte chemotactic proteins - primarily monocytes
Eotaxins (CCL11, CCL24 and CCL26) - eosinophils
Which mechanisms allow the hair follicle to be a site of immune privilege? Name three (for boards)
- Reduction of intraepithelial CD4+ and CD8+ T cells
- Dominance of Treg cells producing IL-10 and TGF-beta
- Expression of FAS ligand within the follicle to delete FAS expressing (potentially autoreactive) T cells
- Downregulation of MHC 1 / 2 expression
- Expression of inhibitory signals (CD200, non-classic MHC class I, etc.)
- Expression of natural immunosuppressants (POMC, a-MSH, TGF-beta, IL-10, IDO, etc.)
- Absent Langerhans cells and presence of functionally altered DC
- Altered trafficking of cells (no direct access to lymphatics in hair bulb, special extracellular matrix)
Sebaceous glands produce cytokines that stimulate which cells in particular?
Th17 cells - involved in defence against bacteria.
In the sensitisation phase of type 1 hypersensitivity reaction, which cells are stimulated in the lymphoid tissue by dendritic cells?
Th2 regulated expansion of B cells producing allergen-specific IgE
In the sensitisation phase of a type 1 hypersensitivity reaction, Igs are bound to the FceR1 on which cells?
Circulating basophils and tissue mast cells
What are the clinical consequences of mast cell degranulation?
Vascular dilation - tissue oedema and
Bronchoconstriction
Local neurological effects - pruritus
The late phase of a type 1 hypersensitivity response involves the influx of which cells?
Eosinophils and macrophages
Which three pathways can mediate a type 2 (cytotoxic) hypersensitivity?
- activation of complement following binding of antibody to target cell with formation of the terminal membrane attack complex and osmotic lysis of the target
- phagocytosis of the antibody opsonized target by a macrophage bearing Fc and C3b receptors
- antibody-dependent cell-mediated cytotoxicity (ADCC) performed by a Natural Killer (NK) cells
What is the most common clinical example of a type 2 hypersensitivity reaction?
A blood transfusion reaction
The same immunological events underlie IMHA and IMTP
How does damage occur during a type 3, antigen-excess, hypersensitivity reaction?
Small Ag-Ab complexes lodge in vessel walls. Inflammation occurs within the vessel wall and endothelial damage may lead to local thrombosis and tissue ischaemia.
Which T helper cells are involved in a type 4 hypersensitivity reaction?
Th1
What are the primary lymphoid organs?
Thymus and bone marrow
Which four mechanisms mediate central tolerance?
- receptor editing
- clonal deletion
- anergy
- development of natural Treg cells
Which four mechanisms mediate peripheral tolerance?
- ignorance
- anergy
- deletion
- development of inducible regulatory T and B cells
Why does the accumulation of dead cells in chronic inflammation help stimulate autoimmunity?
By providing self Ag alongside inflammatory cytokines
What are cryptic epitopes?
Hidden parts of protein molecules (due to physical structure, stereochemical alteration or immune privilege). These can be released/exposed by trauma leading to autoimmunity.
What is molecular mimicry?
Identical sequences of amino acids shared between pathogen and self - the pathogen stimulates an immune response that is then directed at self.
Which complement component, C3a or C3b, is a chemoattractant for neutrophils and activates mast cells?
C3a
Which complement component, C3a or C3b, opsonises bacteria and promotes phagocytosis, activates the membrane attack complex and ‘punches’ holes in some bacterial membranes?
C3b
Which complement component attracts eosinophils?
C5a
In response to mechanical injury, keratinocytes release which cytokine that in turn causes the release of ICAM-1, VCAM-1, E-selectin and other cytokines which attract T-cells?
IL-1
IL-18 is produced by which cells? It acts on Th1 and NK cells inducing their proliferation and production of cytokines such as IFN-gamma.
Keratinocytes
Langerhans cells
Monocytes
Which T cells produce IL-2?
Activated Th1 cells
Which T cells produce IL-4 and IL-13?
Activated Th2 cells = both
NK cells, mast cells and basophils = IL-4
IL-4 stimulates naive T cells to differentiate into what?
Th2 cells
Which cells produce IL-5?
Activated Th2 cells
Mast cells
Eosinophils
Does IL-5 acts on B or T cells?
B cells - to proliferate and produce IgA
Thymic stromal lymphopoetin produced by _________ elicits the differentiation of naive T cells to ____ cells via _______ cells.
Keratinocytes
Th2
Dendritic
Keratinocytes enhance the production of Th2 cytokines from Th2 cells by producing which IL?
IL-33
Are CD4 cells typically found in greater numbers in the dermis or epidermis?
Are CD8 cells typically found in greater numbers in the dermis or epidermis?
CD4 cells predominate in the dermis.
CD8 cells predominate in the epidermis.
CD4 cells interact with which MHC?
MHC2 - present extracellular proteins
CD8 cells interact with which MHC?
MHC1 - present intracellular proteins
What is Prausnitz-Kunstner testing?
Test serum from a hypersensitive individual is injected intradermally into a normal subject; the normal subject is challenged 24–48 hours later with the antigen suspected of causing the immediate hypersensitivity reaction in the hypersensitive individual.
AKA passive transfer test
Fill in the blanks:
During sensitisation, ___, ____, and ____are released from inflamed or injured epithelial cells inducing type 2 innate lymphoid cells (ILC2) to produce ____ and ____.
During sensitisation, IL-25, IL-33 and thymic stromal lymphopoietin (TSLP) are released from inflamed or injured epithelial cells, inducing type 2 innate lymphoid cells (ILC2) to produce IL-5 and IL-13
During sensitisation, antigen presenting cells (APCs) direct the immune response towards helper T cell (Th)2 with production of which cytokines?
IL-4 and IL-13
What is likely to be the major source of histamine and 5-hydroxytryptamine in equine Culicoides hypersensitivity, the Culicoides saliva or the mast cell?
The mast cell
5-HT is responsible for the pain caused by bites and stings from several arthropod species including bees and wasps, yet it has so far not been demonstrated in the saliva of Culicoides.
It is not known whether Culicoides saliva contains histamine.
Second signals are required for T cells to be activated.
ICAM-1 on nucleated and antigen-presenting cells interacts with which adhesion molecule on cytotoxic and helper T cells?
LFA-1 (leukocyte function-associated antigen)
Second signals are required for T cells to be activated.
LFA-3 on nucleated and antigen-presenting cells interacts with which adhesion molecule on cytotoxic and helper T cells?
CD2 (also called leukocyte function-associated antigen [LFA] 2)
Second signals are required for T cells to be activated.
B7-1 on nucleated and antigen-presenting cells interacts with which adhesion molecule on cytotoxic and helper T cells?
CD28
Production of TSLP by primary canine keratinocytes is induced by stimulation with ligands for which TLRs?
TLR-3 and TLR-4
IL-10 can downregulate immune responses or mediate which type of inflammation?
Th2
Which is most heat stable, IgG or IgE?
IgG
The innate immune system comprises of epithelial barriers and their associated secretions, polyreactive antibodies, the alternate pathway of complement and which white blood cells?
Granulocytes, macrophages, natural killer cells and innate lymphoid cells
True or false; The adaptive immune system is specific, slower acting, but more potent than the innate response.
True
Which key cell links innate and adaptive immunity?
The dendritic cell