Immunology Flashcards
I did not put in the stuff that is review!
dendritic cell function
antigen uptake in peripheral sites
antigen presentation
mast cell functions
release of granules containing histimine and active agents
macrophage function
phagocytosis
activation of bacteriocidal mechanisms
antigen presentation
neutrophil function
phagocytosis
activation of bacteriocidal mechanisms
eosinophil function
killing of antibody coated parasites
basophil function
promotion of allergic response
augmentation of antiparasitic immunity
scavenger receptors
help phagocytose
on macrophages
toll like receptors
on macrophages
recognize molecular patterns
ex: flagella
Type 1 interferon response
IFN alpha and beta
antiviral responses
1. cell infected by virus
2. IFNalpha/beta produced
3. induce resistance to viral replication
4. increase MHC class 1
5. activate dendritic and macrophages
6. activate NK cells to kill virus infected cell
7. induce chemokines to recruit lymphocytes
dendritic cell migration/activation
- immature dendritic cells in periperal tissues
- migrate via lymphatic vessels to regional lymph nodes
- mature dendridic activate T cells in lymphoid organs
B cell vs T cell receptor recognition of antigens
T cell recognize epitope that is burried inside protein
antigen must be broken down to be presented on MHC
B cell recognize epitope on surface of protein
T cell receptor complex parts
TCR
* alpha and beta subunits
* recognition
2 CD3 receptors on either side of TCR
ITAMS under membrane
ITAMs
immunoreceptor tyrosine activator motives
under membrane of T cell receptor
controled by phosphorylation
cytosolic pathogens
degraded in cytosol
MHC class 1
presented to CD8
cell death
intravesicular pathogens
degraded in endocytic vesicles
MHC class 2
presented to CD4
activation to kill intravesicular bacteria/parasites
extracellular pathogens/toxins
degraded in endocytic vesicles
MHC class II
presented to CD4
activation of B cells to secrete Ig and eliminate extracellular bacteria
TH1 cells
activate macrophages to kill intracellular bacteria
IFNgamma
TH2 cells
IL-4, IL-5, IL-13
activate eosinophils, mast cells, B plasma cells
B plasma cells
produce antibodies
TFH cells (follicular T helper cells)
causes antibody (isokine) switching on B cells
ex: IgM to IgG
Th17 cells
IL-17
pro inflammatory
recruit neutrophils
Treg cells
inhibit other T cells, dendritic cells
B cell receptor complex
heavy chain, light chain, recognition site (variable)
ITAMS for phosphorylation
functions of antibodies
- neutralization
- opsonization
- complement activation
- ADCC (NK cells)
antibody dependent cellular cytotoxicity (ADCC)
- antibody binds to antigens on surface of target cells
- Fc receptors on NK cells recognize bound antibody
- cross linking of Fc receptors signal NK cells to kill target cell
mast cell activation process
similar to ADCC
1. antibody binds to antigens on surface of target cells
2. Fc epsilon receptors on mast cells recognize bound antibody
3. cross linking of Fc receptors signal mast cells to release granules
types of hypersensitivity
Type I: immediate-type allergic reactions mediated by **IgE antibodies, with mast-cell activation **as the major effector mechanism.
Type II and III: driven by antigen-specific IgG, with the effector mechanisms being antibody-mediated (II) or immune complex-mediated (III).
Type IV: delayed and depicted as being driven by multiple cellular effectors including T cells and myeloid cells.
type 1 hypersensitivity
allergies
onset within minutes of antigen challenge
Th2 and B cell activation leading to memory and plasma cells
plasma cell antibodies cause activation of mast cell degranulation
mast cells function, products
Derived from hematopoietic cells in the bone marrow
Degranulate in response to crosslinking of surface IgE
Products
* Histamine – vasodilation and edema
* Enzymes – destroy parasites, damage tissue
* Leukotrienes and prostaglandin - inflammation
* IL-4 – Increased differentiation of plasma cells and production of IgE
* IL-5 – Recruits and activates eosinophils
urticaria
type 1 sensitvity in the skin
* “Hives”
* Dermal edema
* Most common in the horse and dog, occurs in all animals
* Characteristic of type I hypersensitivity in the skin
* Caused by chemicals, drugs, insect bites/stings
atopic dermatitis
type 1 hypersensitivity
Atopy = tendency to develop type I hypersensitivity reactions
* Genetic predisposition
* Environmental triggers (Pollen, mold, food allergens)
* Chronic pruritus/itching
* Typical lesion distribution
* Rhinitis/stuffy nose and asthma in about 15% of patients
* Differential diagnoses: ectoparasites, infectious dermatitis, flea allergy, food allergy
anaphylaxis
type 1 hypersensitivity
Rare and life-threatening
Dyspnea/difficult breathing
Vomiting, Diarrhea
Collapse
Treatment (species-specific)
* Epinephrine - vasoconstriction
* Diphenhydramine - antihistamine
* Dexamethasone - reduce inflammation
* Fluids – improve circulation
* Terbutaline - bronchodilator
testing for type 1 hypersensitivity
Blood test
* RAST (radio-allergosorbent test)
* Blood sample evaluated for IgE to allergens
Intradermal test
* Inject small quantities of common allergens
* Evaluate for swelling/erythema
Diet testing for food allergies
immunotherapy (allergy shots)
Repeated low dose exposure to allergens
Has been used in cats and dogs
Mechanisms
* Decreased mediator release from mast cells and basophils
* Increased numbers of regulatory T cells
* Fewer Th2 cells
* Treg cells produce IL-10 and TGF-B
* Decrease IgE production
* Suppress mast cells and basophils
Not effective for food allergies
type 2 hypersensitivity
Onset within minutes or a few hours
e.g., autoimmune hemolytic anemia, drug allergies
transfusion reaction
type 2 hypersensitivity
Blood types are based on erythrocyte surface antigens (EAs)
Plasma contains antibodies to antigens NOT expressed on the erythrocytes
* Naturally-occurring (alloantibodies)
* Induced by previous exposure
Signs of transfusion reactio
* Fever
* Hemolysis (Anemia, Icterus/jaundice, Hemoglobinemia and hemoglobinuria, Disseminated intravascular coagulation)
* Allergic (Hives, Itching)
Neonatal Isoerythrolysis in Horses
Type 2 hypersensitivity
* Foal inherits RBC antigen that is foreign to the mare
* Mare sensitized to foal’s erythrocyte antigen during pregnancy, parturition, previous transfusion
* Foal nurses and ingests colostrum containing antibodies to its own RBCs
* Hemolysis
* Also reported in cattle, cats
type 3 hypersensitivity
Can be quick with onset within 2-6 hours
Autoimmune diseases
Arthus reaction
type 3 hypersensitivity
very rare, can occur after 2nd vaccination
1. locally injected antigen in immune individual with IgG antibody
2. local immune complex formation activates complement, sensitize mast cells
3. degranulation of mast cells
4. local inflammation, increased fluid and protein release, phagocytosis, blood vessel occlusion
antigen excess type 3 hypersensitivity
Immune complexes form in the vessels
Deposit in the walls of small capillaries
* Renal glomerulus
* Synovium of joints
* Uveal tract of the eyes
* Epidermal basement membrane
Complement fixation
Vasculitis
Thrombosis and ischemic necrosis
cutaneous vasculitis
type 3 hypersensitivity
Immune complex deposits in the basement membrane of the skin
Common locations
* Pinna
* Paws
* Nose
* Tail
Lesions are:
* Well demarcated
* Often target-shaped (targetoid)
immune mediated glomerulonephritis
type 3 hypersensitivity
Immune complex deposition in glomerular basement membrane
Disrupts filtration barrier
Loss of protein in the urine
* Hypoproteinemia, edema, effusions
* Proteinuria
type 4 hypersensitivity
delayed type
sensitization phase: Inflammation by 2-6 h
effector phase: peaks by 24-48 hours
e.g., poison ivy
Contact dermatitis
type 4 hypersensitivity
poison ivy
delayed response (sensitization then immune response)
tuberculin skin test
test uses type 4 hypersensitivity
1. Identification of animals infected with Mycobacterium sp. (TB)
2. Inject purified fragments of dead mycobacterial bacteria under the skin
3. Wait 3 days
4. Assess for swelling at injection site
autoimmunity definition
inappropriate response of the immune system against self components
can be organ specific or systemic
autoimmunity and hypersensitivity
related to all types of hypersensitivity (esp 2, 3):
1: eosinophilic esophagitis
2: autoimmune hemolytic anemia
3: systemic lupus erythematosus
4: type 1 diabetes
autoimmune thyroiditis
organ specific autoimmune disease
hypothyroidism and hyperthyroidism
autoimmune skin diseases
organ specific
* psoriasis
* pemphigus
* vitiligo
autoimmune hemolytic anemia
organ specific (blood)
different than transfusion reaction (non self)
IgG targets self RBC
rheumatoid arthritis
non organ specific
can cause systemic issues, not just joints
multiple sclerosis
non organ specific
targets myelin, but also systemic
sex bias in autoimmune disease
skewed highky female
female animals have increased severity/incidence
type 1 diabetes
organ specific autoimmune (pancreas)
young onset, insulin dependent
type 1 diabetes stages
Chronic autoimmune disease with strong inflammation
Stage 1:
* Induction by PRR- pattern recognition receptor (TLR, RIG-I) ligands (viral dsRNA, dying cells), activate pancreatic beta cells
* Production of Type I interferons
* upregulation of MHC class 1
Stage 2:
* Activation of macrophages and T cells (Th1, Th17, Tregs)
* Involvement of pancreatic b cells in inflammation (next slide)
* Amplification of inflammation
Stage 3:
* Maintenance or resolution depending on the fate of b cells
* activation of beta cell apoptosis and MHC class 2 presentation leading to more T cell activation
* more inflammatory cytokines produced to futhter activate beta cells apoptosis
inflammation affect on beta cells
Detrimental:
* Suppression of b cell function
* Continued b cell death
* Maintenance of disease
Beneficial:
* Stimulation of b cell proliferation
* For individuals with mild insulitis, inflammation might resolve and normal b cell function be regained
Systemic lupus erythematosus (SLE)
systemic autoimmune disease
mostly effects women of child bearing age
can lead to lupus nephritis (leading cause of death)
treatments: nonselective immunosuppressants
causes of Systemic lupus erythematosus (SLE)
The exact cause of SLE is unknown, but several factors have been associated with the disease.
Genetics: The disease is not linked to a single gene, but people with lupus often have family members with autoimmune conditions.
Environment: Triggers include UV light, certain medications (e.g. antibiotics), viruses, physical or emotional stress, trauma.
Hormones: Women of childbearing age most vulnerable.
criteria for diganosis of lupus (SLE)
- rash
- photosensitivity
- oral ulcers
- arthritis
- serositis (inflammation of lining around lungs or heart)
- kidney disorder
- blood disorder (anemia, leukopenia, lymphopenia, thrombocytopenia)
- immunologic disorder (anti-DNA or anti-phospholipid antibodies)
- abnormal antinuclear antibodies
lupus immunological mechanisms
celiac disease
allergic reaction with autoimmunity features
gluten modified and presented in MHC class 2
activates CD4 T cells, inflammation
general factors contributing to autoimmune disease
genetic (HLA and non HLA genes)
immune (breakdown of self tolerance)
environment (drugs, infection, smoking, hormones, nutrition)
central tolerance
deletion of lymphocytes with self antigens before they are released from generative organs (bone marrow, thymus)
peripheral tolerance
deletion of lymphocytes that recognize self antigens in peripheral tissues
