Immune overview, autoimmunity, and primary immune deficiencies Flashcards
Th1: cytokines produced
IFN-gamma
Th2: cytokines produced
IL-4, IL-5, IL-13
Th17: cytokines produced
IL-17, IL-22, chemokines
IFN-gamma and IL-12 induce what Th subtype?
Th1
IL-4 induces what Th subtype?
Th2
TGF-beta, IL-6, IL-1, and IL-23 induce what Th subtype?
Th17
Th1: immunologic reactions triggered
- macrophage activation 2. stimulation of IgG 3. antibody production
Th2: immunologic reactions triggered
- IgE production 2. activation of mast cells 3. activation of eosinophils
Th17: immunologic reactions triggered
- recruitment of neutrophils 2. recruitment of monocytes
Th1 is used by the host to defend against what?
intracelluar microbes
Th2 is used by the host to defend against what?
helminthic parasites
Th17 is used by the host to defend against what?
extracellular bacteria, fungi
Th1: role in disease
immune-mediated chronic inflammatory diseases (often autoimmune)
Th2: role in disease
allergies
Th17: role in disease
immune-mediated chronic inflammatory diseases (often autoimmune)
Describe each of the four major Ig subtypes
- IgM: low affinity, activates the classical complement pathway 2. IgG: neutralizes microbes and toxins, opsonizes antigens, activates classical complement pathway, responsible for antibody-dependent cellular cytotoxicity (ADCC) 3. IgA: mucosal transport, neutralizes mucosal microbes and toxine 4. IgE: ADCC of parasites, responsible for allergy reaction (mast cell degranulation)
Name the three complement pathways and what is responsible for activating them
- Classical pathway: IgM and IgG 2. Alternative pathway: C3b 3. Lectin pathway: mannose-binding lectin (MBL)
All complement pathways converge on what?
Activation of C5-C9, forming the membrane attack complex (MAC)
Describe APECED
Autoimmune polyendocrinopathy candidiasis ectodermal dystropy (APECED): Cause: AIRE gene defect -> example of failure of central tolerance Autoimmune adrenal and parathyroid disease Can also induce autoimmune hypothryroidism, hypogonadism, vitiligo, and pernicious anemia Also associated with fungal infections (candidiasis)
APECED is caused by what?
AIRE gene defect -> thymic medullary cells do not express self-antigen -> self-reactive T-cells are not deleted (failure of central tolerance)
Name the major clinical features of APECED
- bradycardia, hypotension (salt craving) 2. bronzed skin 3. thrush in mouth 4. abnormal nails
Lab findings of APECED
- low cortisol 2. low calcium, low PTH 3. hyponatremia, hypocalcemia, hyperkalemia
Describe ALPS
Autoimmune lymphoproliferative syndrome (ALPS): Cause: mutations in Fas or FasL -> example of failure of peripheral tolerance Widespread lymphadenopathy, splenomegaly, and autoimmune cytopenias (hemolytic anemia and thrombocytopenia). High IgG, IgA, and IgM common Increased percentages of double-negative T-cells
Clinical features of ALPS
- Pallor 2. diffuse lymphadenopathy 3. splenomegaly
Lab findings of ALPS
- hypergammaglobulinemia 2. Coomb’s positive hemolytic anemia 3. Flow cytometry shows increase double-negative T-cells
ALPS is caused by what?
Mutations in Fas or FasL -> failure of peripheral tolerance
Describe IPEX
Immune dysregulation, polyendocrinopathy, X-linked (IPEX): Due to mutation in Foxp3 gene (loss of Treg cells) Requires bone marrow transplant -> deadly otherwise Affects boys in infancy Hypergammaglobulinemia Presents with IBD, severe eczema and food allergies, T1DM, thyroiditis, autoimmune hemolytic anemia, thrombocytopenia
Clinical features of IPEX
- Diffuse eczematous rash 2. Cachexia 3. Pallor
Lab findins for IPEX
- Hypergammaglobulinemia 2. Coomb’s positive hemolytic anemia 3. IgE ~14,000IU/dl (nl < 200) 4. positive skin allergy test to all (most) foods 5. low serum albumin, iron deficiency 6. hyperglycemia, glucosuria, low insulin
Treg cells express which gene?
Foxp3
What is the Foxp3 gene?
Expressed in Treg cells. It is mutated in IPEX syndrome.
Which gene family is most frequently associated with autoimmune disease?
HLA
Ankylosing spondylitis is strongly associated with which MHC allele?
HLA-B27
Which MHC allele is frequently associated with a wide variety of autoimmune disorders, including: RA, T1DM, pemphigus vulagaris?
HLA-DR4
Name the 4 types of hypersensitivity reactions:
Type 1: immediate sensitivity (IgE-mediated) Type 2: antibody-mediated Type 3: immune-complex-mediated Type 4: delayed-type hypersensitivity (T-cell mediated)
Allergic rhinits, asthma, eczema, and food allergies are ell examples of what type of hypersensitivity reaction?
Type 1
Type 1 hypersensitivity is mediated by what?
IgE
Myasthenia gravis and Graves disease are examples of what type of hypersensitivity?
Type 2
A multinucleate cell found an an inflamed muscle is called a(n)
Aschoff body
What are the criteria for Acute Rheumatic Fever?
J(heart)NES criteria: J = Joints (heart) = heart (carditis) N = nodules E = erythema marginatum S = sydenham’s chorea 2 major or 1 major + 2 minor criteria + supporting evidence of preceding GAS infection major: carditis, polyarthritis, sydengam’s chorea, erythema marginatum, subQ nodules minor: fever, arthralgia, elevated acute phase reactants, prolonged PR interval
Acute rheumatic fever is caused by what?
Molecular mimicry of heart muscle by S. pyogenes virulence factors (M proteins) following GAS infection
Treatment for ARF
Penicillin prophylaxis
ARF is what type of hypersensitivity reaction?
Type 2
Goodpasture’s syndrom is what type of hypersensitivity reaction?
Type 2
Name treatment options for type 2 hypersensitivity reactions
- Non-life-threatening: high dose IVIG, corticosteroids, Rituximab 2. Life-threatening: plasmapheresis