8. Type IV Hypersensitivity Flashcards
Type IV Hypersensitivity: Delayed type hypersensitivity (DTH)
- Involves ____ and ____ immunity
- ____, cytokines and pro- inflammatory mediators
- Reactions ____ or systemic
• Clinical examples:
– Contact ____ test
– Persistent ____ infection
• Antibodies not involved
Hallmark = activation of antigen specific T cells, CD4 - \_\_\_\_ cell or \_\_\_\_ • Presentation of \_\_\_\_ antigen • Cells become activated, produce cytokines, modify or induce an inflammatory rxn by recruiting macrophages or neutrophils • These inflammatory cells cause injury • In addition = CD8 T cells which can recognize processed antigen associated with MHC \_\_\_\_ • Cytotoxic T cells will kill the target cell by inducing \_\_\_\_ • Could be local or systemic • Many forms of DTH ◦ Going to look at contact dermatitis ◦ Persistent intracellular infection: we saw this w/ \_\_\_\_ inflammation
T-cells
cell-medaited
macrophages
localized
dermatitis/tuberculin
intracellular
Th1 Th17 processed class I apoptosis chronic
Type IV Hypersensitivity: Contact dermatitis:
triggered by small molecules > ____ Primary antigen exposure - ____
Contact dermatitis: • DTH that occurs in the skin following contact w/ the antigen • Most of the antigens that cause this disease are \_\_\_\_ • Haptens > can't induce immune reaction > interact with our protein > form \_\_\_\_ > taken up by dendritic cells that reside in epidermis, migrate into draining lymph node > cellular-immune response > \_\_\_\_ lymphocytes (CD4/CD8 cells) that leave the lymph node > produce cytokines that alter \_\_\_\_ permeability • When memory T cells arrive at the scene > first activated by local dendritic cells > takes a few days for reaction to get going **Type I - III are \_\_\_\_ hypersensitivity (minutes - hours) but in type IV, when memory T cells arrive to the scene, they first have to be activated by dendritic cells. This takes a few \_\_\_\_ = delayed type hypersensitivity • First step = processing of antigen, presenting at local site to memory cells, they'll become activated, then they will produce an array of cytokines - either pro-inflammatory or modulate macrophage • Preferentially \_\_\_\_ over neutrophils in these lesions
neoantigen
sensitization
haptens
neoantigens
memory
vascular
immediate
days
macrophages
Th1 derived cytokines activate macrophges—critical to DTH
Activation of ____ cells at local site –> leads to cytokines
• Recruit and activate ____
• Mac’s will produce proteases, pro-inflammatory cytokines (listed), ____ (respiratory burst)
In this situation, there is this ____ antigen
• If the antigen was left alone, it wouldn’t cause any problem
• Rather than be protected (in which case we would refer to it as CMI: cell mediated immunity),
we are dealing with a destructive response (in which case, we will refer to it as DTH)
Th1
macrophages
ROS
inert
Agents that induce contact dermatitis
most are haptens form neo-antigens via modification of self proteins
- Strong detergents or ____
- Skin cleaning products
- Cosmetics or makeup
- ____
- Clothing or shoes
- Household cleaning products
- Formaldehyde and other chemicals
• Rubber or latex • Metals, such as nickel • Jewelry • Perfume or fragrances • Weeds and plants, such as poison ivy or poison oak • Medicinal lotions • Dental materials
* Incomplete haptens, and inert (left alone, they would not do much), but when topically exposed > hapten can combine (reactive to our own proteins) forms \_\_\_\_ (hapten-carrier complex) * Poison ivy - \_\_\_\_ - small molecule on the leaf - some are sensitive to it * \_\_\_\_ can cause reactions, and gold as well * Reaction from socks
soaps deodorant neoantigen catechol amalgams
Clinical signs and symptoms of contact dermatitis
• Skin lesion or rash at the site of exposure
– ____, erythema
– ____ of the skin in the exposed area
– Papules (solid), vesicles, and bullae (fluid filled blisters)
– May involve oozing, draining, or crusting
– May become ____ and thickened, scaly, raw
• Disease: dermatitis; lesion at site, characterized by itching (pruitis) and erythematous • Skin is tender on site of exposure • Solid lesions > papules • Contain vesicles/bulla > fissure bt \_\_\_\_ and \_\_\_\_ > fluid-filled vesicle; vesicle is smaller than \_\_\_\_ ○ Vesicles more often associated with \_\_\_\_ infections, bull more often associated with immune reactions • \_\_\_\_ - not pus! • Indurated and hard, not due to \_\_\_\_
itching (pruritus) tenderness indurated epidermis dermis bulla viral oozing fibrosis
- Catechol is part of leaf > exposed > sensitized > T cells react > formation of complex
- Hypersen > T cells are not reacted to skin by itself, but only if ____ is present (not AID)
- Produce ____ cells > activated > cause damage
- Lesions > you will see ____ cells, ____, ____ (dilated BV)
hapten memory T cytokines inflammation
- Dental pt that was examined wearing latex gloves (left)
- Feet > leather of ____
- ____ clasp reaction
sandals
metal
- ____ can cause reaction, and ____ as well
* Not as bullous as skin lesions
gold
amalgam
Histopathology of Contact Dermatitis
• T cells arrive at local site (starts from dend cells taking up complex, some go to lymph node, but can process \_\_\_\_ > release mediators that start inflam rxn) > BV dilated, and abundance of \_\_\_\_ (not neutrophils) > \_\_\_\_ (BV surrounded by lymphocytes) • No \_\_\_\_ here > just perivascular cuffing • Lymphocytes migrate out of BV into the epidermis > that's where the carrier complex is > in the process: cause damage to epithelium, cause edema in the epidermis > \_\_\_\_ ○ Space bt epithelial cells; formation of spongiotic vesicle (starts off as microvesicle, and eventually gets large) • Hallmark: \_\_\_\_, \_\_\_\_ vesicle, and \_\_\_\_ cuffing (w/o vasculitis)
locally lymphocytes perivascular cuffing vasculitis spongiosis edema spongiotic perivascular
edema
spongiotic
perivascular
- Spongiotic vesicle > larger, and filled with ____
* Nothing more than a ____
fluid
blister
- Blue > stained with reagent that shows T cells; surrounding the ____ and migrating towards the epidermis; encounter ____ cells with hapten carrerir process > spongiosis leads to microvesicles, leads to spongioitic vesicle
- Bulla can be ____ that have fused
BV
dendritic
microvesicle
- Tend to rupture > ulceration > ____ infection
* Treated with ____ lotion (to relieve itching), and if severe reaction > topical ____
secondary
calimi
corticosteroids
• Causes epidermis to slough off > ____ also a problem, in addtion to ____ infection
dehydration
secondary
Type IV Hypersensitivity:
DTH with persistent intracellular microbial infection:
• Viruses:
– ____
– Adenoviruses
– ____
• Bacteria: – \_\_\_\_ spp. – Chlamydia spp. – \_\_\_\_ sppl. – Salmonella spp.
• Fungi: – \_\_\_\_ spp. – Histoplasma capsulatum – \_\_\_\_ – Aspergillus
• Protozoa:
– ____ spp.
– Toxoplasma gondii
– ____ cruzi
• Formation of a \_\_\_\_ • Form of \_\_\_\_ inflammation, but directed by the immune system • Type IV: persistence of pathogen, and it may produce something to make it difficult for inflam response to eliminate it ○ \_\_\_\_ immune response > makes this unique • T cells activated > to a foreign antigen > can produce cytokines > modulate the target cell that's infected (can die), can act on other inflam cells and bring macrophages in, or CD8-cells can be generated to eliminate the antigen ○ Pathogen is \_\_\_\_; the immune system contains instead of eliminates > activates T cells > lesion that walls off infection • Mycobacteria > Tb; 50% of population in US, 33% in world; lack of \_\_\_\_, or people are living much \_\_\_\_; spreads via \_\_\_\_ and exposure to \_\_\_\_
retroviruses
poxviruses
mycobacteria
cornebacterium
candida
cryptococcus
leishmania
trypanasoma
granuloma chronic cellular persistent access closer inhalation conjunctiva
Type IV Hypersensiivity: Tuberculosis
• Etiology: ____ hominis
• Pathogenesis: DTH leading to formation of ____ (tubercles); initially involves ____, but other tissues may be affected
• Signs and symptoms:
– “A ____” that lasts 3 weeks or longer, weight loss, coughing up blood or mucus, weakness or fatigue, fever and chills
• Tx: antibiotics (e.g. ____), drug ____ strains
• Hominis - human strain; bovine strain, reason why milk is homogenized • Initally involves lung; transmitted from infected: cough ○ Starts as pulmonary • Initially, when inhaled > native defense mechanisms: the matter is caught up mucus, brought up by cilia (\_\_\_\_) and you cough it out • Also have \_\_\_\_ macrophage; initially handled, and if it's able to eliminated > no disease ○ Whether or not depends on the \_\_\_\_, the \_\_\_\_ of the strain of myco, and how well the host \_\_\_\_ are able to clear bacteria w/o further activation • Eventually, the bacteria survives (\_\_\_\_), will infect alv macro's intiially, and within a few weeks immunity is developed > T cells arrive and activated produce cytokines, and bc alv macro's are unable to kill internal myco > granuloma forms due to cytokines from T cells > protective mechanism > even with walling out > outcome may be good or bad: wherever the granuloma forms, at expense of normal tissue; in most patients, the myco is eliminated (90%); in subset, the bacteria may be fxnally eliminated, but latent; in even smaller, the disease progresses into Tb • Mycobacterium - \_\_\_\_, not gram+ or gram-
m. tuberculosis granulomas lung bad cough rifampin isoniazid resistant
muco-ciliary escalator alveolar microbial load virulence macrophages
intracellular
acid-fast
