Immunology Flashcards
What cytokine family does IL-31 belong to and which receptors?
IL-31 belongs to the IL-6 cytokine family and is secreted primarily by activated CD4+ helper T cells.
IL-31 acts via a heterodimeric IL-31 receptor and the oncostatin receptor (OSMR).
In dogs, IL-31 can be secreted by T cells after allergen exposure or exposure to bacterial antigens. IL-31 activates the JAK STAT pathway as well as the mitogen activated protein kinase pathway in canine cells.
L-13 is elevated in (disease) but not in (disease)?
IL-13 is elevated in TEN not EM
Define cytokoines?
Cytokines are a broad and loose category of small proteins important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents.
_____ is known to be a major regulatory factor in the production of IgE
IL-4
___ cytokines may play an important role in the acute phase, whereas ___cytokines may be more relevant in the chronic phase.
TH2
TH1
Canine keratinocytes have been shown to produce pro-inflammatory agents such as (list 3) in response to Der f1 and LPS?
granulocyte macrophage colony-stimulating factor
IL-8
Tumor Necrosis factor
What is thymic stromal lymphopoietin?
Is is an IL-7-like cytokine that stimulates dendritic cells to induce naïve T cells to differentiate into TH2 like cells.
(IL4, 5 and 13 in humans/IL-4, 13, 31 in dogs
Damaged keratinocytes produce more ____ and ____ which skews toward a Th2 response, with IgE production and allergic inflammation.
TSLP
Il-33
What is the role of IL-23?
Upregulates IL-22 by Th1, Th17, Th22
Upregulates IL-17
What is the main role of Tarc in allergic inflammation?
Chemokine that dendritic cells produce TARC which recruits CD4 helper T cells to skin.
What is the role of Th2 cytokines in dysregulation of skin barrier function?
Decrease expression of tight junction proteins
Decrease expression of filaggrin
- Increase skin pH (increased proteolytic activity
which degrades ceramides and allows for deeper
penetration of allergens)
- Decreased extrusion of lamellar bodies which leads
to decreased AMP, increase staph colonization and
more inflammation
What chemokines and cytokines are produced by keratinocytes?
IL-1, iL-6, IL-7, IL-8, IL-10, IL-12, IL-15, IL-18, IL-20, TNF, IFN (alpha, beta and gamma)
NK cell can only recognize and detroy a target cell if it fails to express ____ molecules of MHC
class I
What are the two key types of dendritic cells within the skin immune system?
Langerhan Cells (Epidermis) Dermal dendritic cells (Dermis)
What is the main role of Th1 cells?
Helps cell-mediated/cytotoxic responses against viruses or intracellular pathogens
Produce IFN and mediate cell-mediated immunity involving the activation of cytotoxic T cells, NK cells and phagocytic cells.
What in the main role of Th2 cells?
Helps antibody responses against extracellular pathogens
What is the main role of Th17 cells?
Helps responses against fungi
What is the main role of T-reg cells?
Switches off responses that are no longer required
What cytokine(s) do CD4+ Th1 lymphocytes produce?
- IFN-gamma
- IL-2
- TNF-alpha
What cells do Th2 lymphocytes stimulate? Through what cytokine(s)?
B cells
IL-4, IL-5, IL-6, IL-9, IL-13
What are the surface membrane toll-like receptors of the dendritic cell?
TLR-2
TLR-4
TLR-5
What cytokine(s) do CD4+ regulatory T cells produce?
TGF-beta
IL-10
IL-35
What are the cytoplasmic toll-like receptors of the dendritic cell?
TLR-3 viral
TLR 7/8 viral
TLR-9 bacterial
What are the three signals required for activation of a naive Th0 lymphocyte?
1) recognition of antigenic peptide-MHC II complex by the T-cell receptor/recognition of MHC II by the T cell CD4 molecule
2) other surface interactions
3) cytokines produced by the APC binding to receptors on the T cell membrane
Langerhans’ Cell
Primary APC monitoring the body’s external surfaces
Langerin+CCR6+CCR7+/-, radioresistance, slowly self-replicating, highly responsive to CCR6 agonist macrophage inflammatory protein-3α (CCL20)
Mononuclear, dendritic, antigen-presenting cells located basally or suprabasally
Langerhans’ Cell Location
Reside in the suprabasal layers of the epidermis, wedged in between and in close contact with keratinocytes
Account for 3 to 5 % of all nucleated cells in the epidermis of mice and humans
Arranged in a network that occupies the interstices between neighboring keratinocytes
Found in the epidermis, dermis, lymph nodes (usually in the thymus-dependent areas), thymus, mucosal surfaces (oral cavity and bovine rumen)
Distribution varies among species and strains within species
Mouse tail skin & hamster cheek pouch virtually no LCs
Humans: high densities on the head, face, neck, trunk, and limb skin
Density decreases with age, chronic actinic damage
Anchored to surrounding keratinocytes by E-cadherin-mediated homotypic adhesion
Newly discovered population of Langerin+ DCs in the dermis and skin-draining lymph nodes
Distinct phenotypic and mitotic capacities
Dermal Langerin+ LCs do not appear to simply be epidermal LCs en route to the draining lymph node
Langerhans’ Cell Detection
Appear as “clear cells” on routine hematoxyline and eosin stained sections Gold chloride (aureophilic) impregnation allows better visualization and differentiation from other dendritic cells (melanocytes)
Langerhan Cells Morphology
Stellate appearance (why they were initially thought to be of neural origin)
Long cytoplasmic processes that occupy as much as 25% of the surface area of the epidermis
Form a continuous cellular network that surveys the epidermis for foreign antigens via extended dendrites
Convoluted nuclei; clear cytoplasm with no tonofiliments or desmosomes; dose have vimentin
Initially identified by an electron dense organelle: Birbeck granule
Birbeck granules
Also known as Langerhans’ granules
Classic ultrastructural feature of LCs detected in some humans and some animal species by electron microscopy
Consist of superimposed membranes separated by repetitive zipper-like striations
Form by invagination of the plasma membrane and bound antigen
Rod-shaped body with central striations and a saccular terminus (vesicle at one end of the membrane)
Creating a unique tennis-racket appearance
Identified in feline, bovine, ovine, caprine and equine epidermal LCs
**Not found in dog or pig LC (but still have dendritic ATPase + cells)
Function: unclear, but likely includes receptor-mediated endocytosis and transport of cellular materials into the extracellular space
Function in antigen presentation
Birbeck granules: Species specifics
Birbeck granules have been IDed in feline, bovine, ovine, caprine and equine epidermal dendritic cells
In horses: felt to have more than one type – In recent study, lesions for “Kasen” revelaed LCs in the spinous layers had several granules and LCs form the DEJ had a few
In cattle, stain best with alkaline phosphatase
In sheep, stain best with acetyle cholinesterase
In Guinea pigs, mice and humans, stain best with adenosine triphosphatase
In mice & dogs, stain well with non-specific esterase
Surface molecules expressed by LCs
DOGS: CD1a,b,c, CD11a,c, CD18, CD45, ICAM-1, MHC class II, vimentin positive CD4 and CD90 (Thy1) negative
CATS: CD1a, CD4, CD18, and MHC class II positive
CD1a
First monoclonal antibody that clearly identified LCs bound to CD1a
A major histocompatibility complex I-like molecule
Member of the group 1 CD1 proteins (CD1a, CD1b, CD1c)
Presents microbial lipids to T cells
Can be found in high concentration in the Birbeck granule
Langerin (CD207 a well-known surface receptor on Langerhans cells (LC), belongs to the ______ family and constitutes a major pathogen binding receptor able to regulate both innate and adaptive immune responses
C-type lectin receptor (CLR)
Used more recently to specifically recognize LCs – single best feature discriminating LCs from other cells
Expressed in virtually all LCs in stratified epithelia.
A membranous C-type lectin with mannose-binding specificity
Bind mannose and related sugar via Ca+ dependent manner through its carbohydrate-recognition domain. Plays important role in the internalization of cell surface antigens
Recognizes mannosylated ligands found on the surface of a wide range of pathogens, including viruses, bacteria, fungi, and protozoa
Following receptor mediated endocytosis, traffics with CD1a to the Birbeck granule
***Mutation in langerin – deficiency of Birbeck granules
Down-regulated upon LC maturation but detectable levels remain in LCs once they reach cutaneous lymph nodes
FcεRi
A high-affinity receptor for IgE
Presence on LCs at antigen presention in the LN
Associated with Th2-type immune responses characterized by IL-4, IL-5, and IL-13 producing T cells
Aggregation of this receptor on LCs induce the release of various chemotactic factors - IL-16 and monocytes chemotactic protein
Type II transmembrane cell surface receptor
membranous C-type lectin with mannose-binding specificity
Bind mannose and related sugar via Ca+ dependent manner through its carbohydrate-recognition domain
C-type lectin receptor
a receptor that binds glycosylated ligands and has many roles, such as in cell adhesion, endocytosis, natural-killer-cell target recognition and dendritic-cell activation
Movement of LC
Epidermal LCs are continuously replaced from a resident precursor pool throughout life under steady-state conditions
Half-life (non-inflamed murine epidermis): 2 – 3 months
Two non-mutually exclusive pathways fro repopulation:
1. LC division within the epidermis
2. Differentiation of LCs from skin-resident or blood-borne precursors
Describe migratory LCs
LCs migrate to draining LNs in the steady state
After leaving the epidermis - migrate through dermal lymphatic vessels and localize in T-cell area of skin draining lymph nodes
Upregulate and redistribute MHC class II molecules, upregulate the expression of CD40 and CCR7 (CC-chemokine receptor 7 - essential for LC migration to skin draining LNs)
LC Maturation
Best characterized in context of inflammation but also can occur in the steady state
When stimulated, LCs retract the dendritic processes, detach from surrounding epithelial cells and migrate out of the epidermis
The capacity to process protein antigens via MHC class II pathway is down-regulated, however the ability for T-cell co-stimulation is improved
Review:
↓ expression of Fc Receptors, Birbeck granules, and E-cadherin decreases the ability for antigen capture & processing
LPS, TNF-α lead to an upregulation of CCR7 that induce migration from the skin to the lymph node by ligating chemokines MIP-3β and SLC
β2 integrins are upregulated to help binding to other cells and ECM
Functional properties of LC
LCs carry antigens, including self-antigens, from epidermis to the draining LN
Functions as antigen-processing cells in the epidermis, having the capability to process native antigens and activate memory and effector-T cells monitoring the skin surface
After LC has migrated from the epidermis, LC alters phenotypically, showing a decrease expression of endosomal antigens and acquiring molecules which enable it to interact with unprimed T cells
One of these molecules is ICAM-1
LCs: T cell stimulation
- APCs present the processed protein/glycolipid using MHC class I and II and CD1; which in turn interact with TCR on CD4+ and CD8+ T cells
- Accessory molecules of the B7 family creates co-stimulatory signal
B7 (CD80) binds CD28 on the lymphocyte
CD40 binds CD40L on the lymphocyte
Other co-stimulatory molecules include:
ICAM-1 (CD54) that binds to LFA-1 (CD11a/CdD18)
LFA-3 (CD58) binds to CD2 (LFA-2)
LC: Immune Tolerance
LCs have a role in the transport and presentation of skin antigens to the skin-draining LNs under steady-state conditions
Treg cells are induced by immature DCs key role in maintaining tolerance to self-antigens in the periphery; exact mechanism is unknown
Dermal DCs
Reside in the dermis
Do not have Langerin expression and Birbeck granules
Express more MHC class II molecules and lack phagolysosomes when compared to macrophages
During inflammatory conditions, DC types not normally cutaneous residents (plasmacytoid DCs) will appear
No single or specific marker for these cells; phenotypically less well characterized
CD11c – probably best tool we currently have to identify them
CD1b and CD1c
CD90 also stains for dermal dendritic cells, not LCs
CD11c-
indicates that these may be derived from circulating DC precursors migrating into the skin due to inflammatory and chemotactic signals
BDCA-2
The only marker that is exclusive for pDCs
Follicular Dendritic Cells: (FDCs)
Cells with membranous projections present in the germinal centers of lymphoid follicles in the lymph nodes, spleen and mucosal lymphoid tissues
Not derived from precursors in the bone marrow and are unrelated to dendritic cells that present antigens to T lymphocytes
Trap antigens complexed to antibodies or complement products and display these antigens on their surfaces for recognition by B lymphocytes
This process is important for the selection of activated B lymphocyte who antigen receptors bind the displayed antigens with high affinity
Dendritic cells and disease states
‘Pathogenesis in contact hypersensitivity’
Sensitization phase: a low molecular weight electrophilic/hypdrophilic haptens penetrate the skin and form hapten-protein complexes with epidermal carrier proteins = the complete antigen
These binding proteins are likely cell surface molecules on LC (MHC class I and II molecules) - LC maturation occurs
LCs migrate to the LN, where the antigen is presented to T cells that then develop into Th2 cells secreting IL-4, IL-5 and IL-13 .
These cytokines lead to activation of eosinophils and isotype switching and IgE production B cells.
Mast cells degranulate upon cross-linking of surface-bound IgE antibodies by the allergen.
Endothelial cells are activated and express adhesion molecules that allow binding and exocytosis of inflammatory cells
T cells secrete cytokines and eosinophils release their granules leading to inflammation and clinical signs
• Important role in afferent phase (Induction/presentation and processing of antigen) of contact hpersenistivity (a type IV hypersensitivity reaction)
• Immunological reaction to hapten
o Poison Ivy Wandering jew plant Jasmine Cedar Chips
o Medications Neomycin Thiabendazole Tretinoin Miconazole
• Hapten-protein complex binds to epidermal Langerhan’s cells, dendritic cells and is then pinocytosed.
• Antigen is digested into small polypeptides that bind to MHC II and are transported to cell surface.
• Langerhans cells dendritic network become rounded and decrease in number after contact with chemical sensitiser and produce IL-1β
• Migration to lymph node occurs within 2-4hr and there are changes in cellular adhesion molecule expression to facilitate this.
• Presentation of MHCII peptide-Ag to naïve T cells leads to clonal proliferation of specific T cells in lymph nodes
• Effector and memory T cells are then released in to circulation
The main role of ____ is to activate allergen-specific T lymphocytes via MHC II / T cell receptor interactions.
LCs
Epidermal LC are _____ in number in skin biopsies from lesions of human AD and canine AD.
Increased
LC possess ______ which facilitates the uptake of IgE associated allergens.
FcεRI (high affinity IgE receptor)
A recent study demonstrated that canine LC express ____ chains but not the ____ chain of FcεRI which is identical to humans
α and γ
β chain
(Murine LC do not express functional FcεRI (only express γ chain; therefore canine is a better model) (Bonkobara et al 2005 Vet Research Communications 29;499-505)
Insect bite hypersensitivity in the horse have an increased number of what cell type?
increased number of LC
LCS and interaction with UV
Following UV light exposure, epidermal LCs are decreased in density and altered morphologically, resulting in an immunosuppressive environment and antigen-specific tolerance
UVB causes LC apoptosis leading to a dose-dependent decrease of LCs in the skin
UVAI – induces emigration of DDCs from the skin
UVAII – decreases the number of LCs
LCs and drug interaction with GC, CSA, Tacrolimus and imiquimod
GCs (topically or systemic) depress LCs numbers and function
Tacrolimus/pimecrolimus causes apoptosis-induced depletion of T cells and decrease of inflammatory DCs
CsA impairs DC migration by regulating chemokine receptor expression and inhibiting COX-2 expression
CsA and tacrolimus inhibit MHC-restricted antigen presentation pathways of DCs
Imiquimod induces migration of LCs from skin to draining LN
What is the most reliable way to identify LC?
Electron microscopy; antibody stain Lag-antigen
What are LC Histochemical Staining in different species?
Cow LC’s stain best for ALP
Sheep LC’s stain best for acetyl cholinesterase
Human, guinea pig and mouse LC’s stain with ATP’ase
Mice and Dogs also stain with non-specific esterase
Antigen is encountered and processed by LC and then presented (altered) by the MHC complex. Cellular adhesion that allows this is via ____ and ____.
ICAM-1 & LFA (lymphocyte function-associated antigen)
What are LFAs?
are in the immunoglobulin superfamily of adhesion molecules
***Also the T-cell LFA-2 (also called CD-2) binds to LFA-3 on APC
What is ICAM-1?
is an integrin from the surface of most hematopoietic cells and antigen presenting cells
Histiocytoma
a. Early lesions: Phenotype similar to immature LCs
i. –High levels: CD1, E-cadherin
ii. –Low levels: MHC I and II
b. Regressing lesions: Phenotype similar to mature LCs
i. –Down-regulation CD1, E-cadherin
ii. Up-regulation MHC I and II ICAM-1
LC in delayed hypersensitivity
Antigen or hapten associates with MHC II of LC’s
These travel to regional LN and settle in paracorticol T-cell area
T-cell activation occurs
Activated T-cells are supported by continuous release of IL-1 by the LC
Activated T-cells release IL-2 which results in continued proliferation of activated T-cells
These are released into circulation and when an individual is challenged keratinocytes release cytokines (IL-1, IL-8 and TNF-α), which results in increased endothelial adhesion molecule expression (L-selectin/ELAM 1), which promotes activated memory T-cell migration into the skin.
Migrating T-cells release, among others, γ-interferon, which promotes continued keratinocyte cytokine release. Both CD4+ and CD8+ T cells are present in contact hypersensitivity.
What are ‘touch spots’?
areas within glabrous skin where MCs are clustered near unmyelinated sensory nerve endings at the bottom of rete ridges
Innervated by a single, slowly adapting type 1 nerve fiber
Other terms: hair disc, touch dome, touch corpuscle, Iggo disc
In hairy skin and whisker pads – concentrated to rete ridge and outer root sheath of hair follicle at sites of attachment of the arrector pili muscle
Function of merkle cells?
Characterized as slow-adapting mechanoreceptors, which are confined to the tylotrich pads of mammalian skin
Slowly adapting type 1 neurons – a subset of Aβ (mechanoreceptive fibers) touch receptors with a low threshold value
Other functions suggested:
1. Neuroendocrine functions such as influencing cutaneous blood flow and sweat production via the release of vasoactive intestinal peptide
Can produce: serotonin, enkephalin, VIP, somatostatin, calcitonin gene-related peptide
Merkel Cells are innervated what what type of fibers?
Innervated by myelinated type I nerve fibers, which forms a structure called a Merkel cell-neurite complex
Tylotrich pads
Tylotrich hairs
Special type of tactile hair found in mammalian skin
Larger then regular hair follicles
Contain a single stout hair and an annular complex of neurovascular tissue that surrounds the follicle at the level of the sebaceous glands
Each tylotrich hair follicle is associated with a Tylotrich pad
Tylotrich pads are composed of a thickened and distinctive epidermis covering a convex area of fine highly vascular and innervated connective tissue
Immunohistochemical markers of the Merkel cell
K8, K18, K19, and K20 keratin peptides
K20 is restricted to Merkel cell in skin and therefore is most reliable marker
Merkel Cell Tumors
This is a primary cutaneous neuroendocrine tumor
Can be either malignant and metastatic or benign with rare recurrence after surgery
Commonly found on lips, ears, digits, oral cavity
Usually rapid growing +/- ulceration
Extremely rare in cats- case reports of benign nasal tumor and malignant tumor in dorsolateral cervical region
Function of merkle cells?
Slow adapting mechanoreceptors
Type I mechanoreceptors aka myelinated type I nerve fibers
Located in sites of high-tactile sensitivity
Unmyelinated nerve endings which are slow adapting touch receptors are associated with Merkel’s cells
Influence cutaneous blood flow
Influence sweat production
Via release of vasoactive intestinal peptide
Coordinates keratinocyte proliferation
Maintains and stimulates stem cell population of the hair follicle
Controls hair cycle
What does gamma delta refer to?
γδ refers to a type of T cell receptor
Disulfide-linked heterodimer; expressed on T cells that don’t have the more traditional αβ T cell receptors
γδ TCR is associated with CD3 and ζ proteins just like lymphocytes with αβ receptors
How are gamma delta T cells made?
• Develop in the thymus
- Lineage separate from the αβ T cells but they have a common precursor
• There is very little diversity in the γδ TCR, which suggests that the ligands (the stuff this receptor recognizes) are invariant and conserved
But still adapative since rearrange TCR genes and develop memory
Who has gamma delta T cells?
Epithelial tissues of certain species
50% of the lymphocytes in the small bowel mucosa of mice and chickens are γδ T cells.
Majority of T cells in mouse skin are γδ T cells
What is the function of gamma delta T cells?
Do not recognize MHC-associated peptides
Some γδ T cells can recognize small phosphorylated molecules, alkyl amines or lipids such as those found in mycobacteria and other microbes when they’re presented on “class I MHC-like” molecules
Some studies have shown that M. tuberculosis can stimulate γδ T cells.
Other γδ T cells recognize protein or nonprotein antigens that do not require processing or an APC.
Antimicrobrial immunosuvalience
Produce IFN gamma
Cytotoxic functions
Antigen Presentation to CD8+ and CD4+ cells
Anti-Tumor Immunosurveilance
Produce IFN gamma
Down regulate protumor alpha beta T cells
Have NKG2D molecule surface molecule that targets cellular destructions
T regulatory Functions
Expression of Fas ligand
Wound healing
Clinical importance of gamma delta T cells?
Canine epitheliotrophic cutaneous T cell lymphoma is most often caused by T cells that express the γδ receptor rather than the αβ receptor.
Lymphocytes that infiltrate the epidermis and dermis of atopic dogs can express both γδ and αβ receptors. In the dermis of atopic dogs, there are 10x more αβ than γδ receptors. In the epidermis of atopic dogs, some cases have a mostly γδ lymphocyte population. People with AD do not have an increase in γδ lymphocytes in their skin.
Subsets of γδ T-cells are able to produce IL-4 or IFN-γ
γδ T-cells can recognize antigens directly without prior processing
Ruminant γδ T-cells recirculate continuously between epithelial surfaces, such as skin or intestinal epithelium, and the bloodstream
Birbeck granules
variously described as being zipper, rod, flask or tennis racket like in appearance. They form by invagination of the plasma membrane and bound antigen, thus providing the morphologic description of the mechanism by which Langerhan cells internalize surface-bound antigen for processing and representation at the surface.
Langerhan cells are aureophilic meaning….
They stain with gold chloride. Unlike Langerhan cells in humans, those in dogs and cats are S-100 protein and ATPase negative.
In dogs, Langerhan cells are positive for what markers?
CD11a,c Vimentin CD1a,b,c CD18 CD45 ICAM1 MHC2
How can you distinguish Langerhan cells from dermal dendritic cells?
They are CD4 and Thy1 (CD90) negative
In cats, Langerhan cells are positive for what markers?
CD1a, CD18, CD4 and MHC2
Following UVL exposure, Langerhan cells are ____ in density and altered morphologically.
decreased
What are examples of PAMPs?
peptidoglycan, lipopolysaccharides (LPS), glycolipids, and mannin-rich carbohydrates.
On what cells are TLRs found?
macrophages, eosinophils, mast cells, dendritic cells, and epithelial cells.
What is an iron binding protein found in the stratum corneum where its main affect is to limit the amount of free iron build up which can predispose to bacterial infections?
transferrin
It can also reduce the binding of gram-positive and ram-negative bacteria to surfaces.
It is currently not known if this mechanisms is relevant to canine and feline skin BUT transferrin has been show to inhibit growth of Malassezia in vitro.
What is a common peptide with antibiotic functions produced by the epidermis?
defensins
These are systemic-rich proteins that are also present in neutrophil granules. Synthesis of defenses is unregulated in response to inflammatory cytokines such as IL-1 and TNF. Defensins are similar to broad spectrum antimicrobials - able to kill bacteria and fungi.
Expression of what antimicrobial peptide was down regulated in skin of atopic drop and may be therefore a link to the increased incidence of bacterial infections in atopic dermatitis.
Canine b-defensin
This process known as ____, it is the first step in any infection. Bacteriahave specific molecules on their surface known as ___ that allow them to do this.
adhesion
List common adhesions on staphylococci:
teichoic acid
lipoteichoic acid
fibronectin binding proteins
laminin binding proteins
***these molecules bind to various proteins on the host such as fibronectin, laminin and collagen.
If the basic barrier mechanisms of the epidermis are unable to prevent injury to the host, the innate immune system has a number of other defense mechanisms that can be used to provide protection against parasites or infectious agents. The mechanisms include:
Activation of complement
Recruitment and activation of phagocyte cells (neutrophils and macrophages)
Recruitment of eosinophils
activation of intraepithelial lymphocytes and natural killer cells
production of cytokines and chemokine
____ system is a series of plasma proteins that exist in the quiescent state until they are activated. The role of this system is to assist the immune system in eliminating pathogenic bacteria.
Complement
The complement cascade can be activated by three distinct pathways
- classical pathway
- alternative pathway
- lectin pathway
Describe the classical complement pathway
The classical pathway is activated by antibody-antigen complexes, which bind to the first complement component, C1. Is the subsequent complex series of steps, C4 and C2 components of complement bind to C1 forming the active enzyme = C3 convertase
What enzyme catalyses conversion mod the third complement component (C3) into C3a and C3b?
C3 convertase
What complement protein is a chemoattractant for neutrophils and can activate mast cells, whereas __ can opsonize bacteria and promote phagocytosis.
C3a
C3b
What protein activates that membrane attack complex (MAC) , which is a cylindrical structure composed of complement components 5,6,7,8,9. The membrane attack complex can ‘punch holes’ in the membrane of certain types of bacteria, resulting in cell death.
The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b.
How is the alternative complement pathway activated?
It is activated by direct interaction between the surface of a microbe and C3b, which is generated in the serum by slow, spontaneous hydrolysis of C3. Once bound, the C3b catalyses further conversion of C3 into C3b.
Describe the lectin pathway
A plasma lectin bind to a mannose residue on the surface of a microbe and activated c1 in the absence of antibodies. The pathway is subsequently the same as the classical pathway.
Deficiency in C3 occurs in both humans and what breed of dogs? This results in increased susceptibility to pyogenic infections.
Brittany spaniels
Deficiencies of the components that make up the membrane attack complex only lead to increase rates of infection by what organism, leading to meningitis in humans?
Neisseria
To eliminate bacteria, initially, what circulating cells are first recruited to the site of infection?
neutrophils and monocytes
The initial inflammatory response is triggered by resident tissue ____ that detect microorganisms and secret the pro inflammatory cytokines IL1 and TNFa.
macrophages
What cytokines lead to the up regulating of adhesions molecules on blood vessel walls, including selecting and interns, which can bind to ligand on the inflammatory cells.
IL-1 and TNFa
