Skin & Immune Mediated Disease 2 Flashcards
what are the cells and effector mechanisms in innate immunity
cells: sentinel cells –> macrophages, mast cells, dendritic cells
effector mechanims: inflammation, complement activation
what are the important cells and effector mechanisms
cells: antigen presenting cells: dendritic cells, macrophages
effector mechanism: antibody-mediated (humoral immunity), cell-mediated, immunological memory
how are innate and adaptive immunity linked
pathogens can be phagocytosed via primitive “non-specific” mechanisms
mononuclear phagocytes (monocyte/macrophages) can process antigen and “present” it to the immune system (ex. antigen presentation)
antigen presentation triggers the activation and expansion of –> 1. B cells producing antibody specific for the antigen 2. cytotoxic T cells are able to lyse cells infected with the pathogen
what are the 2 key attributes that adaptive (acquired) immunity develops in response to antigens present on invading organisms
- specificity
- memory
what are the skin immune systems
- physicochemical barriers (stratum corneum, surface lipids, antimicrobial peptides –> defensins, cathelicidins)
- skin microbiome (the commensal microorganisms in the skin, have an anti-inflammatory role, affect T cell maturation –> educate T cells, priming them to respond to similarly marked pathogenic cousins)
how does the cornified envelope form
loricrin (80%), involucrin
filaggrin breaks down to amino acids (natural moisturizing factor)
how does the lipid bilayer form
forms lipids –> extruded from lamellar bodies
what rivets the corneocytes together
corneodesmosomes –> structural integrity
what does filaggrin form from
profilagrin (keratohyalin granules) –> causes keratins to aggregate
lipids for in lamellar bodies
what % of healthy stratum contains lipid
85% lipid
sphingolipids (ceramide)
cholesterol
free fatty acids
what do sphingolipids and fatty acids contribute to
- physical barrier
- permeability barrier
- immunologic barrier
which cutaneous lipids have antimicrobial properties
sphingoid bases derived from epithelial sphingolipids
mechanisms are not fully understood
what produces antimicrobial peptides
ex. defensins, cathelicidins
produced by neutrophils, macrophages, epithelial cells and by bacteria
what is the function of antimicrobial peptides
- activate and recruit inflammatory cells
- alarm and arm keratinocytes
what is the skin microbiome
the skin like the gut needs microbial signals and proper immune function
commensal microbes (ex. staph epidermidis) stimulate skin and immune cells to produce IL-1
IL-1 activates T cells which become more responsive to invading organisms
what are the factors affecting skin microbiome
- host physiology (sex, age, site)
- environment (climate, geographical location)
- immune system (previous exposures, inflammation)
- host genotype (susceptibility genes such as filaggrin)
- lifestyle (occupation, hygiene)
- pathobiology (underlying conditions such as diabetes)
what is the role of commensal bacteria (microbiome) in innate immunity
- facrtors produced by commensal bacteria modulate the skin immune system
- staphylococcus epidermidis produces –> antimicrobial peptides, small molecules which enhance expression of defensins
what are the cells of the skin immune system
- keratinocytes (squames)
- dendtritic cells
- mast cells
- lymphocytes (T cells)
what are the functions of keratinocytes (squames)
account for the majority of epidermal cells
mitosis of stem cells in s. basale
important in keratin production
what are the function of dendritic cells
major role in antigen presentation
epidermal (Langerhan cells)
dermal
what are the functions of mast cells
release histamine
what are the function of lymphocytes (T cells)
various T-helper subsets
what are chemokines and cytokines
chemokines: critical in T cell and macrophage recruitment
cytokines: arm effectors and direct the immune response
what are the roles for keratinocyte
- sentinel cell activate in host defence –> express pattern recognition receptors (PRRs) respond to DAMPs and PAMPs (associated with microbial invasion)
- pro-inflammatory effector cell –> reacts to harmful insult –> producing a complex mixture of AMPs, pro-inflammatory cytokines and chemokines
- non-proffessional antigen-presenting cell –> expresses MHC class II molecules can interact with antigen-experienced T cells
what is the innate immune response to injury or pathogen invasion
- release of primary cytokines –> inflammation –> upregulation of endothelial expression of adhesion molecules –> recruitment of additional innate effector cells
- activation of skin cells and resident innate immune cells –> langerhan’s cells & dermal dendritic cells carry antigen to draining lymph node
what are the adaptive immune response in the skin
- memory T cell carry TCRs specific for antigen previously encountered in skin
- interaction of antigen specific T cells with APCs results in T cell activation
- cytokines stimulate expression of T cell specific chemokine ligands on endothelium
- T cells recruited by antigen non-specific mechanism
what are langerhans cells and what is their function
epidermal dendritic cells
dendritic cells link the innate and adaptive immune responses
langerhans cells interact with skin resident memory T cells
what is the response of the epidermis to injury
release of pro-inflammatory cytokines & growth factors by keratinocytes
–> altered proliferation & differention (hyperplasia, hyperkeratosis/parakeratosis)
what is the response of the dermis to injury
stimulation of dermal inflammation (erythema, inflammatory edema, exudation)
–> release of secondary cytokines/growth factors promotes further change –> antigen presenting cells interact with T cells
what is the are epidermal responses to injury (7)
- orthokeratotic hyperkeratosis
- parakeratotic hyperkeratosis
- hypergranulosis
- acanthosis
- hyperplasia
- hyper- or hypopigmentation
- lichenification
what is orthokeratotic hyperkeratosis
increase in thickness of anuclear surface keratin
what is this
orthokeratotic hyperkeratosis
increase in thickness of anuclear surface keratin
what is this
parakeratotic hyperkeratosis
thickened keratin layer has retained nuclei
what is this
hypergranulosis
prominent granular layer associated with hyperkeratosis
what is this
acanthosis
broadening of the spinous (prickle cell) layer –> often accompanies hyperplasia
what is this
hyperplasia
an increase in the number of cells often irregular
what is this
altered pigmentation
pigmentary incontinence
what is this
lichenification
hyperkeratosis, hyperplasia and dysplasia
what are examples of direct traumatic skin disease
- friction/pressure
- chemical (irritant contact dermatitis)
- heat (burns)
- light (phototoxicity)
what are the indirect causes of traumatic skin disease
metabolic (photosensitivity)
what is self trauma
major contributing factor in the development and progression of skin disease in animals
what is self-trauma a response to (2)
- response to pruritus (or pain)
–> action of various mediators, epidermal & dermal sensory nerves
- scratch reflex –> spinal reflex, modulated by motor cortex neurons
what is the itch-scratch cycle
what is hairless plaques (acral lick dermatitis)
self trauma in skin disease
also known as lick granuloma
may reflect underlying pyoderma
may be an indication of behavioural disturbance
how do you distinguish orthokeratotic from parakeratotic hyperkeratosis
???
are antimicrobial peptides good or bad
?
what is the skin microbiome and how does it help
?
what is this cell and what is its role in protection of the skin
is this cell part of the innate or activated immune response
?
which epidermal changes result in thickening of the skin
?
which immune cell can be of myeloid or lymphoid origin
?
what are the differential features of innate and adaptive immunity (self/non-self discrimination, lag phase, specificity, diversity, memory)
innate:
self/non-self discrimination: present, reaction is against foreign
lag phase: absent, response is immediate
specificity: limited, the same response is mounted to a wide variety of agents
diversity: limited, hence limited specificity
memory: absent, subsequent exposures to agent generate the same response
adaptive:
self/non-self discrimination: present, reaction is against foreign
lag phase: present, response takes at least a few days
specificity: high, the response is directed only to the agents that initated it
diversity: extensive, and resulting in a wide range of antigen receptors
memory: present, subsequent exposures to the same agent induce amplified responses
