4.1 Immunodeficiency and hypersensitivity Flashcards
primary immune deficiency:
- inherited genetic defects in immune response genes
- typically seen in young animals
secondary immune deficiency:
- acquired immune deficiency
- typically seen in adult aniamls
primary innate immune: Canine leukocyte artesian deficiency (CLAD)
- occurs as a result of a mutation in CD18 gene
- CD18 is an integrin (cell-adhesion) molecule necessary for neutrophil extravasation and phagocytosis
- recurrent bacterial infections in the presence of a marked neutrophil
Without CD18 neutrophils can’t?
can’t get out of the blood and get into the infected tissues
primary adaptive immune deficiencies: Equine SCID
- autosomal recessive mutation
- defect in a DNA repair enzyme required for antigen receptor gene recombination
- no functional T or B cells
- highly susceptible to infection
- usually die by 4-6 months from bronchopneumonia / sepsis
If a lymphocyte cant make an antigen receptor what happens?
it dies
Foul immunodeficiency syndrome:
- profound anemia and immunodeficiency
- B lymphocyte deficiency and lack of antibody production
- genetic test now developed to identify carriers
Canine X-linked SCID:
Basset hounds and corgis
- X-linked: 50 % of males born to carrier females are affected
-usually die from pneumonia or sepsis
interleukin 2:
cytokine responsible for driving the proliferation of naive T cells when they recognize antigen
Mutation in IL-2R:
- extra C in code
- all AA acids that are translated beyond that point are wrong and quicly come to a premature STOP codon - short and stumpy
selective IgA deficiency of german shepherds associated with:
- IBD
- anal furunculosis
- disseminated aspergillosis
**common theme = weak muccossal immunity system
retrovirus-induced immonsuppression:
-acquired later in adult life
- FeLV
- FIV
toxin-induced immunosuppression:
- toxic substances
- drugs
- lead
can lead to immunosuppression:
- malnutrition
- stress
- chronic disease
- immunosenescence (system fails with age)
___ is an immunosuppressive hormone
Cortisol
Immunosuppressive drugs:
- corticosteroids
- ciclosporin
- chemotherapy drugs
Only given for short periods of time
When to suspect immunodeficiency?
- animal suffering from repeated infections that relapse following therapy
- animals infected between 3-12 months of age, especially if known breed-suceptability
immunological tolerance:
- sometimes the immune system deliberately ignores or suppresses responses to some antigens
- strategically targeted immune suppression
immune tolerance: (we don’t want to attack)
foreign antigen from HARMLESS environmental component
- food antigen, airborne antigen, contact antigen
self-antigen
- ubiquitous protein, tissue-specific protein
when a foreign antigen pathogen is detected what is expected?
immune activation, clearance of orgainism
foreign pathogen + immune tolerance =
persistent infection
immune tollerance: mucosal disease
- bovine viral diarrhea virus (BVDV)
- pregnant cow infected –> calf becomes immunotolerent to BVDV and persistently is infected
foreign environmental antigen (harmless) + tolerance =
healthy
foreign environmental antigen (harmless) + immune activation =
allergic disease
self antigen + tolerance =
healthy
self antigen + immune activation =
autoimmune disease
central tolerance:
- clonal deletion of most autoreactive T cells occurs in the Thymus
- some self-reactive T cells are reused and forced to become regulatory T cells (natural Tregs)
Thymus decide:
what T cells are useful nd helpful
peripheral tolerance:
- immunological ignorance (T cell never meets antigen
- clonal anergy to harmless antigens in the absence of “danger” signals
- active suppression by induced Tregs
Thymic selection of T cells: borderline
can only grow to become regulatory T cells not inflammatory T cells
anergic:
unresponsive to further antigenic stimulation
Active suppression: regulatory T cells
- selected in Thymus (natural Tregs) or developed in secondary lymphoid tissues (induced Tregs)
- military police of the immune system
what do regulatory T cells produce?
natural immunisuppressive cytokines (ex: IL-10 calm immune system) upon activation
hypersensitivity:
an inappropriate, hyperactive immune response to an antigen
- tolerance mechanisms fail
- can lead to immune-mediated disease
ex:
harmless environmental antigen = allergy
self antigen = autoimmunity
Type 1 hypersensitivity:
- immediate type hypersensativity
- abnormal production of IgE (Only parasites) to an environmental antigen (allergen)
-Mast cells become sensitized and when triggered attack as if it were a parasite infection when it isnt - ‘anti-parasite’ response upon subsequent exposure to allergen
True or false: You CAN’T have an allergic reaction the first time your exposed to something?
True, must generate IgE antibodies first and they have to get up to a sufficient concentration and bind to surface mast cells
Hypersensativity I: Sensitisation Phase:
- associated with a lack of tolerance for that allergen
- induction of high levels of T helper 2 cells-driving class switching of our B cells towards producing igE
- igE then coats the surface of the mast cell and becomes sensitized
Hypersensativity I: Re- exposure and reaction phase:
- Allergen comes in and binds to surface IgEs
- Mass cell degranulates and releases loads of cytokines, chemokines, and inflammatory mediators like histamine
- This produces an acute inflammatory reaction
** can see further cellular infiltration from eosinophils which produce inflammatory mediators and make things worse
Type II hypersensitivity:
- production of IgM or IgG to cell surface antigens or extracellular matrix proteins
- “neutralization” blockade of receptors
- an immunological attack on target cell (opsonization and complement)
Red blood cells (common target)
- neonatal isoerthroysis: mares antibodies attack foul red blood cells
- autoimmune hemolytic anemia
Feline infectious anemia:
the pathogen doesn’t cause disease the immune system does - when an antibody tries to kill the pathogen it loses red blood cells
Type III hypersensitivity:
- antibody IgG binding to soluble antigen
- deposition of immune complexes in blood vessels
Vasculitis: ( inflammatory rxn in blood vessels)
- Drug reaction (antibiotics)
- Wet FIP
- Glomerulonephritis (BV in kidneys)
- immune-mediated polyarthritis
Cutaneous drug reaction:
Cutaneous vasculitis associated with hypersensitivity (IgG) to some drugs (ex: sulphonamide antibiotics
Huge problem in hypersensitivity III:
- formation of immune complexes in the vasculature
- creates degree of clotting
- leads to fluid leakage into tissues and creates inflammatory reaction at this site
Type IV hypersensitivity:
- delayed-type hypersensitivity (DTH)
Either caused by:
- abnormal CD4 T cells:
-abnormal CD 8 T cells:
Abnormal CD4 T cells:
- abnormal activation of macrophage in healthy tissues
- macrophage production of inflammatory mediators and MMP enzymes causes tissue damage
Abnormal CD8 T cells:
- killer T cells destroy healthy cells mistakenly thinking that are infected by a virus
- They think Self antigen is a virus
Which hypersensitivities are mediated by antibodies?
Hypersensativity 1, 2, and 3
Hypersensativity Type 4 is mediated by?
T cells
Hypersensitivity IV: sensitization phase
- Happens before inflammatory reaction
- abnormal production of T helper type 1 cell (TH1 Cells)
- instead of becoming regulatory anti-inflammatory cells they become pro-inflammatory TH1 cells
- leave lymphoid to search for infected macrophage
Hypersensitivity IV: re- exposure and reaction
- TH 1 tells macrophage it’s not harmless its a pathogen and needs to produce a massive inflammatory reaction
- local inflammatory response develops at the site and requires T cells to find macrophages and tell them to make cytokine
- This takes 24-72 hrs for signs of inflammation to appear at this site
TB Test:
- delayed-type hypersensitivity test
- measure initial skin thickness
- inject PPD ( mycobacterium avian and bovine)
- measure skin thickness again 72 hrs later
There are several tolerance mechanisms that try to prevent inappropriate immune reactivity. When they fail we may see:
- pro-inflammatory defense systems come into play in the absence if infection
