Viral infections & Hypersensitivity reactions Flashcards

Question

What marker expression and TFs characterize follicular helper T cells in antibody responses?

Answer 1

TFH characterized by expression of CXCR5, ICOS, PD1 - CXCR5 is required to enter the germinal center, interacts with CXCL13 TFs: Bcl-6, IL-21 and IL-6R

Answer 2

The adaptive immune system need to constantly adapt to highly changing antigens

Answer 3

Spanish influenza (1918) caused by H1N1, ~40 million deaths Surface glycoproteins: - hemagglutinin (HA) - neuraminidase (NA) Antigenic drift → constant change in antigenicity of HA and NA owing to point mutations

Answer 4

Slow shift in antigenicity of HA and NA owing to point mutations → leading to Abs not recognizing the antigen anymore (Abs/adaptative immune response needs to adapte) Can also involve sudden emergence of a new subtype of influenza through reassortment of ssRNA strands - Recombination in the reservoir host → big shift in virus → no longer recognized

Answer 5

Expression of harmful immune responses to antigens that are not derived from infectious pathogens (innocuous environmental antigens) Allergies (immediate hypersensitivity reactions) are usually associated with generation of IgE Includes diverse diseases

Answer 6

*All manifested at mucosal barriers 1. Inhaled materials - Plant pollen, feces of very small animals, mold spores, etc. 2. Injected materials - Insect venoms, vaccines, drugs, therapeutic proteins 3. Ingested materials - Food, orally administered drugs 4. Contacted materials - Plant leaves, metals, synthetic chemicals in industrial products

Answer 7

The "allergic atopic march" refers to the progression of allergic diseases that typically starts in infancy with atopic dermatitis (eczema), often progressing to food allergies, and then potentially developing into allergic rhinitis (hay fever) and asthma later in childhood, essentially describing a natural sequence of allergic conditions as a person grows up; it's also simply called the "atopic march" or "allergic march" because "atopic" refers to a genetic predisposition to allergies. 1. Eczema (atopic dermatitis) 2. Food allergy (~1 yo) 3. Allergic rhinitis (hay fever ~ 3 yo) 4. Asthma (~ 6yo)

Answer 8

- Suggests an environmental etiology - Increasing evidence that early-life exposure to a biodiverse microbial environment is crucial for the proper development of the immune system “Hygiene Hypothesis”: reduced early-life exposure to pathogens leads to increased atopy & risk for allergies

Answer 9

"old friends" hypothesis: early life microbiota has an important role in the development of tolerogenic immune functions “Hygiene Hypothesis”: reduced early-life exposure to pathogens leads to increased atopy & risk for allergies Expanded version on the hygiene hypothesis which focuses on all aspects of microbiota, not just pathogens

Answer 10

1. Breast milk 2. mode of delivery (vaginal vs caesarian) 3. Antibiotic use at early age 4. Family size (more pathogen exposure) 5. Interaction with farm animals, pets *Microbiota includes the skin microbiome, nasopharynx microbiome, lung microbiome, gut microbiome

Answer 11

Increase: Peanut-containing oils put on kids with eczema → the peanut antigen is encountered in a context of inflammation and T cell response Decrease: Oral peanut consumption → lots of tolerance mechanisms in the gut

Answer 12

To fight these following factors: 1. Helminths 2. Venoms 3. Noxious compounds 4. Envrionmental irritants Allergies are mis-directed responses → generation of Abs against non-pathogens Are allergies simply misdirected anti-worm responses or do they serve a purpose? Propose that type 2 responses are response to get you to remove yourself from noxious stimuli. They maybe served an evolutionnary purpose beyond expulsing parasites (weep and sweep version)

Answer 13

Type I: - IgE - Soluble antigens - Mast-cell activation Type II: - IgG - Antigen = Cell- or matrix-associated antigen → complement, FcR+ cells - Antigen = Cell-surface receptor → Abs alters signaling Type III: - IgG - Soluble antigens - Complement, phagocytes Type IV: T cell responses to soluble antigens (further elaboration in other flashcards)

Answer 14

- Predisposition to become IgE-sensitized to environmental allergens (atopy) - Prerequisite for type I hypersensitivity reaction is that the person makes IgE antibody when he/she first encounter the first Ag. (context of 21st encounter is important) - IgE binds irreversibly to Fc receptors on mastcells (leading to degranulation), basophils and eosinophils. - IgE antibody causes allergic reactions because of its exceptionally high affinity Fc receptor and cellular distribution of the receptor. (Fc ε RI). *All IgE-mediated responses involve mast cell degranulation

Answer 15

Predisposition to become IgE-sensitized to environmental allergens in type I hypersensitive reactions

Answer 16

Symptoms vary depending on the site of encounter of the allergen → eaten vs injected This will influence the site of mast cell degranulation

Answer 17

Der p1is found in dust, it has its own enzymatic activity 1. The enzyme Der p1 cleaves occludin in tight junctions and enters mucosa (in the lungs) 2. Taken up by resident DCs for antigen presentation and Th2 priming (in lymph nodes) 3. Th2 cells induce B-cell switch to IgE production 4. Plasma cell travels back to mucosa and produces Der p1-specific IgE antibodies 5. IgE binds to Fc eplisonR1 receptor on mast cells 6. Der p1-specific IgE binds to mast cells; Der p1 triggers mast cell degranulation 7. Mast-cell degranulation contents cause allergic symptoms

Answer 18

Mast cells reside in nearly all tissues, mature locally - found in connective tissues, often surrounding blood vessels or lymphatics - can release mediators which impact vasculature as well as spreading to distal sites via the blood or lymph Large cells found that have secretory granules containing inflammatory mediators - Bind monomeric IgE (no degranulation, resting) - In a second contact with the Ag, it cross-links 2 IgE bound molecules on the mast cell and triggers rapid degranulation and the release of histamine. - Degraunlates very quickly (~20-30mins) Mast cell activation in allery orchestrates a broad inflammatory cascade with pathophysiological consequences

Answer 19

No, the antigen specificity is confered by IgE and the mast cells binds non-specifically to cross-linked IgE Assay: Take a mast cell → coat it with IgE and cross-link them in an non-antigen specific way → mast cell degranulates

Answer 20

Mast cell activation orchestrates a broad inflammatory cascade with pathophysiological consequences - Downstream inflammatory cascades - Cytokine production → epithelial mucous production + smooth muscle constriction - Immune cell recruitment - Release of histamine (→ endothelial vascular leakage), Proteases, Eicosanoids etc. Ex: runny nose is due to mast cell degranulation

Answer 21

1. Gastrointestinal tract: Increased fluid secretion, increased peristalsis Leading to → Expulsion of gastrointestinal tract contents (diarrhea, vomiting) 2. Airways: Decrease diameter, increased mucus secretion Leading to → Congestion and blockage of airways + Swelling and mucus secretion in nasal passages 3. Blood vessels: increased blood flow, increased permeability Leading to → Increased fluid in tissues causing increased flow of lymph to lymph nodes, increased cells and proteins in tissues, increased effector response in tissues

Answer 22

IgE mediated mast cell activation → recruitment of basophils, eosinophils, Th2 CD4 T cells, B cells → amplify the response Eosinphils: - Granule release - Synthesis of mediators such as prostaglandins, cytokines, leukotrienes - Amplify mast cell/basophil activation Th2 cell production of GM-CSF & IL-5 leads to greater production of eosinophils by the bone marrow (Amplification)

Answer 23

Introduction of allergen directly into bloodstream can cause a systemic reaction called anaphylaxis Causes can be: drugs (penicillin), food (peanuts), insect stings Symptoms range from urticaria (hives) to fatal anaphylactic shock Anaphylactic shock = reduction in blood pressure → inadequate supply of blood to organs → organs shutting down Treated with Epinephrine

Answer 24

Epinephrine is used to treat anaphylactic shock: - Stimulates the re-formation of tight junctions between epithelial cells - Relaxes constricted bronchial smooth muscle - Stimulates the heart *Preventing organ shut down

Answer 25

1. Genetically inherited - Multiple different genes can be involved ex: chemokines, antimicrobial peptides, epithelial barrier, genes from epithelial airway, involved in CD4 Th2 responses, PRRs, etc. 2. Envrionmental Both need to be combined

Answer 26

Assessed by skin testing - Introduction of potential allergens - Mast cells degranulation and release of histamine → Development of a wheal and flare withing minutes

Answer 27

Antibody-mediated cytotoxic hypersensitivity, Immune reactant = IgG Antibodies to foreign antigens on cells leads to destruction of cells - Cell death is via activation of complement or via phagocytosis of the cells recognized by Fc receptors Ex: Transfusion reactions, hemolytic disease of the newborn Can be side-effects seen after the administration of certain drugs (eg. penicillin): hemolytic anemia

Answer 28

*Type II hypersensitivity response 1. Penicilin binds to surface of RBC creating neoantigen which is recognized by immune system 2. Red cells that have been covalently bonded to complement-coated penicillin are phagocytosed by macrophages 2. Macrophages process the penicillin-modified protein and present peptide to specific CD4+ T cells 3. CD4 T cells stimulate penicillin-specific B cells to secrete Abs 4. Abs bind to RBCs Responses: 1. Binding of Ab to penicillin-modified red cells makes them susceptible to complement lysis (Ag- Ab complex). 2. Phagocytosis via Fc receptors and complement receptors

Answer 29

These types of reactions are caused by immune complexes formed by IgG and soluble Ags Ex: Serum sickness Pathology is due to the deposition of these antigen:antibody aggregates and initiation of an inflammatory response The pathogenic potential of immune complexes is determined by their size, the amount and isotype of antibody

Answer 30

Early response → little Ab and excess antigen → small immune complexes are formed that do not fix complement and are not cleared from circulation *The smaller complexes are less efficient to fix complement, they circulate in the blood and become deposited in blood vessel walls Intermediate stages in the response → similar amounts of Ab and Ags → large immune complexes are formed that can fix complement and are cleared from the circulation Late in the response → large amounts of Abs and little Ag → Immune complexes of intermediate size are formed that can fix complement and are cleared from circulation *complexes when Ab is in excess are easily eliminated by complement and macrophages

Answer 31

Disease caused by type III hypersensitivity depends on the route of delivery and the site of immune complex deposition - Local hypersensitivity reaction in the skin triggered by subcutaneous injection is called an Arthus reaction - Local hypersensitivity reaction in the lung is called farmer’s lung - Systemic hypersensitivity reaction can be triggered by injection of large quantities of a poorly catabolized foreign antigen and is called serum sickness

Answer 32

local type III hypersensitivity reaction in the skin triggered by subcutaneous injection is called an Arthus reaction Rare, localized type III hypersensitivity reaction, often occurring after vaccination, characterized by a painful, hard swelling, redness, and potentially ulceration or necrosis at the injection site

Answer 33

systemic type III hypersensitivity reaction that can be triggered by injection of large quantities of a poorly catabolized foreign antigen Involves formation of Ag:Ab complexes Can lead to uticarial rashes

Answer 34

Systemic type III hypersensitivity reaction → Rituximab-induced serum sickness Symptoms = rashes, low blood pressure, flu-like symptoms Rituximab is a monoclonal Ab therapy used to treat lymphoma (anti-CD20) - Chimeric Ab made of murine variable sequence + human constant region Binding of antibody to CD20 results in lysis of B cells via complement, or phagocytosis - Can trigger formation of large immune compelxes leading to type III hypersensitivity

Answer 35

Reactions mediated by antigen-specific effector T-cells (Th1 CD4 T cells and CD8 T cells) → release of type 1 IFN and other cytokines Also known as delayed-type hypersensitivity reactions (DTH) because they occur 1 to 3 days after contact with Ag - This time course contrasts with those of antibody-mediated hypersensitivity, which appear after few minutes The amount of Ag required to elicit type IV hypersensitivity reaction is 100 to 1,000 greater than that required for antibody-mediated sensitivity Ex: chronic graft rejection, poison ivy, tuberculin skin test

Answer 36

Mantoux test, standard tuberculin test Intradermal injection of 0.1 mL Intrduration measured 48-72 hrs later 1. Ag is injected into subcutaneous tusse and processed by local APCs 2. TH1 effector cells recognize antigen and releases cytokines which acts on vascular endothelium 3. Recruitment of phagocytes and plasma to site of antigen injection causes visible lesion *The presence of these antigen-specific T cells suggest you are infected with tuberculin or that you have been vaccinated recently

Answer 37

Antigen is processed by tissue macrophages → stimulates TH1 cells *AMPLIFICATION of the local reaction 1. Chemokines → macrophage recruitment to site of antigen 2. IFN-y → Activates macrophages increasing release of inflammaotry mediators 3. TNF-a and Lymphotoxin → local tissue destruction, increased expression of adhesion molecules on local blood vessels 4. IL-3/GM-CSF → Monocyte production by bone marrow stem cells

Answer 38

- Occurs by direct skin contact - Caused by small, highly reactive molecules that can penetrate the skin (cross barrier to get access to immune cells) and react with self-proteins - Bind covalently as haptens to skin proteins which become antigenic, are taken up by APCs, processed, and haptenated peptides can be presented by MHC-II → Leads to Th1 cell activation (sensitization and then elicitation) Common example in USA is poison ivy → contains lipid soluble pentadecacatechols in its urushiol oil that can cross cell membranes → Formation of vesicles, influx of monocytes, macrophages & lymphocytes, erythema Other examples: nickel sensitization (nickel metal ions act as haptens)

Answer 39

Chronic condition of the upper small intestine cause by a CD4 T cell response directed against gluten (complex of proteins present in wheat, oats and barley) Elimination of gluten from diet restores normal gut function but must continue throughout life - Strong genetic predisposition (HLA-DQ2 allele, tells you it is CD4-related) *Also has properties of autoimmunity

Answer 40

1. Gluten is broken down into smaller peptides in the gut and absorbed 2. Inside enterocytes, tissue Transglutaminase (tTG) modified gliadin peptide 3. Modified gliadin peptide now has high affinity for the HLA-DQ2 MHC molecule (normally would not bind to MHC-II molecules) - TG is also generating auto-Abs (can screen for these anti-TG Abs to check for celiac disease) 3. The bound peptide activates gluten-sepcific CD4 T cells 4. The activated T cells can kill mucosal epithelial cells by binding Fas - Also secrete IFN-y which activates the epithelial cells 5. Local immune response destroys the villi in the intestinal epithelium, leading to loss of epithelial cells that cover the villi and normally absorb nutrients 6. Intense inflammatory infiltrate in the lamina propria **Autoimmune feature: autoantibodies against tissue transglutaminase gluten-specific helper T cells → help activate glutentTG complex-specific B cells → anti-tTG Ab production

Answer 41

TH1 cells react to soluble antigens → macrophage activation (IFN-y) → chemokines, cytokines, cytotoxins Ex: Contact dermatitis, Tuberculin reaction TH2 cells react to soluble antigens → IgE production, eosinophil activation, mastocytosis (through IL-4, IL-5) → cytotoxins, inflammatory mediators Ex: Chronic asthma, chronic alleric rhinitis Cytotoxic T Lymphocytes → Cell-associated antigens → Cytotoxicity Ex: Graft rejection

Answer 42

Group I - dsDNA → use their dsDNA genome to directly transcribe mRNA. Group II - ssDNA → convert their ssDNA genome into a dsDNA intermediate before mRNA production. Group II dsRNA → one strand of their dsRNA genome is used as a template for mRNA synthesis by a viral RNA-dependent RNA polymerase. Group IV - ssRNA+ → where their ssRNA genome can directly serve as mRNA. Group V - ssRNA- → requiring a viral RNA-dependent RNA polymerase to transcribe their ssRNA genome into mRNA. Group VI - ssRNA-RT → use reverse transcriptase to convert their ssRNA genome into a DNA intermediate (provirus) before integrating into the host genome and producing mRNA.