Immuno Flashcards
A mother brings her 6-year-old son to the pediatrician with a 7 week history of cough and shortness of breath. The mother says that his cough is dry and worse at night when it sometimes wakes him up from sleep. The cough has not been associated with a fever and growth charts reveal that he is growing well. Past history is significant only for travel to many countries on vacation over the last few years. Physical exam reveals end expiratory wheezing and the finding shown in Figure A. The most likely cause of this patient’s symptoms is an example of which of the following types of disorders?
Type I hypersensitivity
Type II cytotoxic hypersensitivity
Type II non-cytotoxic hypersensitivity
Type III hypersensitivity
Type IV hypersensitivity
This patient with cough and shortness of breath who presents with wheezing and eczema most likely has asthma, which is a type I hypersensitivity reaction.
Type I hypersensitivity is caused by antigen cross-linking of IgE on sensitized mast cells. This causes the release of vasoactive mediators (e.g., histamine, leukotrienes, and prostaglandin D2) and inflammatory mediators (e.g., TNF-alpha and leukotriene B4). This mechanism is responsible for asthma, allergic rhinitis (hay fever), anaphylaxis, angioedema, urticaria, and allergies to medications and food. Asthma, in particular, is characterized by cough and shortness of breath that is worse at night and associated with end-expiratory wheezing.
Figure A demonstrates the characteristic appearance of an atopic dermatitis rash. These rashes frequently present as erythematous plaques and papules around the flexor surfaces of the elbows and knees.
Urticaria pathogenesis and presentation
It is almost always a hypersensitivity disorder.
Type 1 hypersensitivity (IgE mediated mast cell degranulation)
presentation of raised red itchy plaques mostly on trunk and extremities
pathogenesis of hereditary angioneurotic edema
cause is genetic by AD transmission → C1 inhibitor deficiency → classical complement pathway has “no breaks” → excess secretion of bradykinin (mediator of edema)
what is the specific immunological mediator of edema
bradykinin
mn: Brady sounds like Brody which sounds like the name of a swol football player
Stevens-Johnson Syndrome and toxic epidermal necrolysis are both variants of which type of skin disorder
Erythema Multiforme (an acute inflammatory dermatosis)
what are the types of immunce cells present in the epidermis versus the dermis
- Epidermis: keratinocytes, Langerhans cells intraepithelial lymphocytes (IELs) provide first line of defense in the outer epidermal layer
- Dermis: T cells, dendritic cells, macrophages, and mast cells
What are the GENERAL descriptions of the 4 types of hypersensitivity responses?
what is the hallmark of type I reaction
degranulation of mast cells
what type of hypersensitivity reaction is shown
Type 1
what type of hypersensitivity reaction is shown
Type II
_________is a marker of mast cell degranulation
tryptase
____and _______antibodies induce hypersensitive reactions
by activating complement.
IgG and IgM antibodies, induce hypersensitive reactions
by activating complement.
what two types of antigens most commonly initiate a Type II hypersensitivity reaction
- self
- drug
Which hypersensitivity reactions present within 1-3 hours of exposure to antigen?
Types II and III
What are the type(s) of immune cells that are responsible for Type III HSRs
Helper T cells and Cytotoxic T cells
- Polyarteritis nodosa
- Poststreptococcal glomerulonephritis
- Serum sickness
- Arthus reaction
- Systemic lupus erythematosis
- Hypersensitivity Pneumonitis (Farmer’s lung)
These are all examples of what type of HSR
Type III
what type of 1 hypersensitivity reaction is characterized by cough and shortness of breath that is worse at night and associated with end-expiratory wheezing.
asthma
what is the characteristic presentation of an atopic dermatitis rash.
These rashes frequently present as erythematous plaques and papules around the flexor surfaces of the elbows and knees. Excoriations, scaling, and vesicles can sometimes be seen.
Of note, infants often have lesions on the cheeks, scalp, and extensor surfaces while older children and adults have lesions on the flexor surfaces.
In _________ (which HSR) reactions, antigen-antibody complexes deposit in healthy tissues, initiating localized inflammatory responses in these tissues.
Type III
Type ____ hypersensitivity reactions are cell-mediated. In these reactions, T-cells are sensitized to an antigen. On subsequent exposure to that antigen, effector T-cells and macrophages will be activated.
Type IV
Examples of type IV hypersensitivity reactions include type I diabetes mellitus, multiple sclerosis, and Hashimoto’s thyroiditis.
Name an environmental risk factor for lupus
Type I diabetes mellitus, multiple sclerosis, and Hashimoto’s thyroiditis are all examples of which hypersensitivity reactrion
Type IV
idiopathic thrombocytopenic purpura is caused by what type of antibodies
anti-platelet antibodies
Antibodies against neutrophil proteinase 3 are also called ____
(PR3-ANCA/c-ANCA) - a type of antineutrophil cytoplasmic antibody (ANCA) that has a diffuse cytoplasmic staining pattern on immunofluorescence studies. These antibodies are most commonly found in patients with granulomatosis with polyangiitis.
Polyneuropathy and melena - what small/medium size vasculitis could be the cause
Polyneuropathy and melena are features of polyarteritis nodosa. This condition is not typically associated with antineutrophil cytoplasmic antibodies. However, antibodies against myloperoxidase or proteinase-3 (p-ANCA) are found only in rare cases.
what is this
p-ANCA staining
what immune system element mediates opsonification of bacteria and immune complexes
C3 –> C3b
terminal complement deficiency leads to what specific breakdown in immune response
Deficiency of factors C5-9 (terminal)–> Defective formation of the membrane attack complex (pokes holes in cells) –> susceptibility to Neisseria
what is the immune response in intracellular pathogens
Intracellular pathogens are best controlled by cell-mediated immune responses, which are orchestrated by T helper-1 (TH1) cells.
Effectors of cell-mediated responses include cytotoxic T cells (CD8+), natural killer cells, macrophages
- cytosolic intracellular pathogen –> MHC I presentation
- phagosomal intracellular pathogen (e.g. TB)–> MHC II presentation
what is the type III HSR
Immune complex-mediated complement activation is the mechanism of a type III hypersensitivity reaction, which is characterized by the deposition of IgG-antigen complexes in various tissues. Examples of type III HSR include polyarteritis nodosa, post-streptococcal glomerulonephritis, IgA nephropathy, and lupus nephritis.
what is the type 1 HSR
IgE-mediated mast cell activation is the mechanism underlying type I hypersensitivity reactions (including anaphylaxis)
t/f Viruses do not cause hypersensitivity reactions
TRUE
in what places of the thymus do negative and positive selection occur
negative selection occurs in the medulla
positive selection occurs in the cortex
AIRE gene product mediates __________
negative selection of T cells
it is a transcription factor that causes medullary thymic cells to express antigens found in other parts of the body (tissue-restricted antigens) on MHC class I and MHC class II receptors. T cells that express T-cell receptors with a high affinity for MHC receptors bearing these self-antigens undergo apoptosis or become regulatory T cells (Treg).
where does V(D)J recombination of B cell immunoglobulin heavy chain gene segments occur
this occurs during the maturation of B cells from lymphoid stem cell precursors within the bone marrow. This process is mediated by VDJ recombinase, an enzyme encoded by the recombination activating genes 1 and 2 (RAG1 and RAG2). The rearrangement of the immunoglobulin DNA segments is antigen-independent and random, thus ensuring a high diversity of immunoglobulins expressed on the surface of B cells and allowing for the collective recognition of a wide variety of antigens.
Autosomal-recessive RAG1 and RAG2 loss-of-function mutations are a rare cause of severe combined immunodeficiency.
what is the MOST important immune factor in the formation of granulomas
IFN-gamma bevause it activates macrophages which are critical for granuloma formation
Pathogenesis of Hyper IgE syndrome (aka Job syndrome)
mutation (AD) in STAT3 causing impaired JAK-STAT signaling –> defective T cell differentiation –> specifically Th17 –> impaired neutrophil migration –> recurrent skin and sinopulmonary infections without inflammation but with mast cell histamine release –> hyper activation of eosinophils and IgE
the other Ig levels are normal and there is a low Th17 count but normal leukocyte count. also the abscesses are painless d/t absence of inflammatory processes
mn: IgE is secondar-E to impaired to neutrophil response
IgM’s main function is to ________________________
initiate the complement system
T cell–independent method of B cell activation is utilized in what immune response
eosinophila can be caused by:
(mn: PACMAN Eats)
- Parasites
- Asthma
- Chronic Adrenal Insufficiency
- Myeloproliferative disorders
- Allergy (Type 1 HSR)
- Neoplasia (Hodkins lymphoma)
- Eosinophilic granulomatosis with polyangiitis
also MI after 12-24 hours
pathophysiology of allergic contact dermatitis
it is a type IV HSR
Phase 1: sensitization phase = “migration of hapten-activated Langerhans cells to regional lymph nodes”
Phase 2: re-exposure: Langerhans cells (cutaneous antigen presenting cells) present antigen (hapten) to sensitized T cells –> cytotoxic T cell response within 2-3 days of exposure
function of IL-6
IL-6 is primarily produced by macrophages and is an acute-phase reactant responsible for the creation of a pro-inflammatory state after a traumatic or infectious stimulus. IL-6 promotes B cell and neutrophil production as well as the release of stress hormones such as cortisol into the blood.
vs IL-8 which does neutrophil chemotaxis (not production)
function of IL-8
IL-8, also known as neutrophil chemotactic factor, promotes neutrophil chemotaxis and phagocytosis at sites of infection in innate immune response. It also promotes the respiratory burst necessary for killing pathogens.
This cytokine is produced at the site of a skin infection by epithelial cells, endothelial cells, smooth muscle cells, and macrophages
vs IL-6 which does neutrophil PRODUCTION (not chemotaxis)
vs IL-17 is the main chemotactic factor for recruiting neutrophils in adaptive immunity (ie via T cell activation)
n.b. C5a (from complement system) also does attraction of neutrophils
mechanism of H. Influenza B vaccine
The major virulence factor of Hib is its polysaccharide capsule, which is composed of the polymer polyribosylribitol phosphate (PRP) → protects the bacterium against phagocytosis and complement-mediated lysis by binding factor H, a circulating regulator protein that normally prevents complement (C3b) deposition on host cells.
The conjugate Hib vaccine is composed of PRP conjugated to a protein toxoid → host development of anti-PRP antibody, which leads to improved opsonization and complement-mediated phagocytosis.
pathogenesis of superantigen mediated T-cell activation
Superantigens bypass regular processing and presentation by APCs and directly connect the MHC class II molecule on APCs to the T-cell receptor on T-cells by forming a bridge outside of the normal binding sites → nonspecific T-cell activation → rapid activation of excessive numbers of T cells → massive cytokine release
*they don’t need to match the antigen-specific MHC II binding site
pathogens assoc: S. Pyogenes (streptococcal TSS) and S. aureus (staphylococcal TSS, of which there is menstural and non menstural types)
