Immunology Flashcards

Question

What are the cells that are involved in a TB granuloma?

Answer 1

macrophages, monocytes, multinucleate giant cells (formed by fusion of macrophages) and lymphocytes

Answer 2

Form of chronic inflammation, response to offending agent that is difficult to eradicate, characterised by organised collection of immune and other cells and aggregation of activated macrophages. Seen in TB, crohns and sarcoidosis.

Answer 3

Foreign-body granuloma - Reaction to inert foreign material (e.g., silica, sutures) - No T cell-mediated immune response Immune granuloma - Caused by agents that are capable of eliciting a T cell mediated response - Certain mycobacterial, fungal and parasitic infections produce immune granulomas

Answer 4

healing by fibrosis and consequent tissue and organ damage. They can calcify over time which is a type of scarring

Answer 5

Nature of damage and nature of tissue

Answer 6

(continually dividing) can easily regenerate as long as there are stem cells remaining e.g., surface epithelium, haemopoietic cells in the bone marrow

Answer 7

do not actively proliferate in their usual state but are capable of (limited) regeneration in response to injury e.g., endothelial cells, smooth muscle cells, parenchymal cells of some solid organs

Answer 8

are terminally differentiated and unable to regenerate e.g., neurons, cardiac myocytes

Answer 9

Existing, surviving functional cells proliferate. Stem cells located in specific niches in the tissue differentiate into the required lineages. Growth factors, produced at the site of injury by macrophages, epithelial cells and fibroblasts, drive the response

Answer 10

Transforming growth factor beta Fibrobalast migration Collagen synthesis Monocyte migration

Answer 11

Platelet derived growth factor Fibroblast migration and proliferation collagen synthesis monocyte migration angiogenesis wound contraction

Answer 12

Vascular endothelial growth factor Angiogenesis (endothelial cell migration and proliferation)

Answer 13

Epidermal growth factor Epithelial cell migration and proliferation, fibroblast proliferation, MMP synthesis

Answer 14

Fibroblast growth factor Fibroblast migration and proliferation, epithelial migration and proliferation, MMP synthesis, wound contraction

Answer 15

• Infection (prolongs inflammation) I • Disease (diabetes causes poor perfusion) Don’t • Nutritional Status (protein deficiency) Need • Glucocorticoids (less inflammation, less repair) Gloves • Mechanical Factors (physical disruption) My • Perfusion (reduced delivery of materials) Pinky • Foreign-bodies (persistent stimulus) Finger • Injury type and extent (loss of function) Itches

Answer 16

**Causes** - Ageing – ‘inflammaging’. Immunosenescence and mitochondrial dysfunction likely contribute - Poor diet. Alteration of the gut microbiome and excess adipose tissue - Stress. Prolonged elevation of cortisol promotes inflammation and attenuates tissue repair **Consequences** - Sickness behaviours and physiological responses, such as fatigue and raised blood pressure - Breakdown of tolerance leading to autoimmune diseases and IMID - Dysregulation of normal cellular and tissue physiology, predisposing to metabolic diseases and cancer

Answer 17

Immunodeficiency- poor or no response to pathogens Autoimmunity- inappropriate response to self antigens

Answer 18

- Smoking - Chemicals - UV - Infection

Answer 19

Some antigens are hidden within cells or are altered in changing environmental conditions (e.g., hypoxia). These appear differently in the bone marrow and thymus and therefore look like non-self in the periphery. These are cryptic antigens. They can activate T and B cells to cause damage and further antigen release

Answer 20

Some pathogen antigens structurally resemble self antigens and may bind BCR/TCR with higher affinity. Infections can activate cross reactive responses to self antigens and initiate autoimmunity. Eg. Ankylosing spondylitis and guillian-barre syndrome

Answer 21

T and B cells with low affinity for self-antigen escape selection and go to the periphery. Antigen alone cannot activate these cells. Inflammation/ infection causes co-stimulatory molecules to be expressed by antigen presenting cells (APC). These APC overcome T cell anergy. The T cells become activated and attack self

Answer 22

Immune reactions to infection or self-antigens leads to damage to self-cells.This can lead to release and presentation of more cryptic self-antigens or normal self-antigens at unusually high concentrations. This can lead to activation of more T and B cells of different specificities – the immune response spreads

Answer 23

Some autoantigens are also DAMPs (Toll-Like Receptor ligands) – such as unmethylated CpG nucleic acid. Host unmethylated CpG usually only becomes available during cell death (apoptotic chromatin). If the unmethylated CpG is not cleared quickly, a self-reactive B cell could receive signals through the TLR and BCR - and become activated

Answer 24

Cytotoxic t cell

Answer 25

Infiltration of neutrophils. Also: evidence of edema in tissue, vascular congestion.

Answer 26

Central necrosis in caseating immune granulomas; no necrosis in non-caseating immune granulomas. Aggregation of macrophages with different phenotypes: multinucleate giant cells, foamy macrophages, epithelioid macrophages. Lymphocytes - generally arranged outside the main aggregation of macrophages

Answer 27

Small intestine- loose mucus layer (not as well differentiated), digestive factors, shorter transit time, paneth cells produce more AMPs, less pathogens [compared to large intestine]

Answer 28

Antigen delivered via M cells, via transcytosis of ab-ag conjugates, via directly sampling from gut and via uptake of apoptotic cells

Answer 29

T cells in Peyer's Patches; and IELs (intraepithelial lymphocytes). Th17 cells are a component of normal epithelial defense; aberrant lumen, Th17 generation linked to immune-mediated inflammatory disease

Answer 30

T-dependent (CD40L, TGF-B) and T-independent (BAFF, APRIL- produced by dendritic cells)

Answer 31

Donor is screened for infectious diseases and feces turned into a preparation for administration. Infused into recipient through nasoenteric tube, enema or colonoscopy. Also oral capsules

Answer 32

Acetate - Substrate for synthesis of cholesterol and long chain fatty acids (LCFAs)in the liver - Modulates the activity of immune cells Propionate - Substrate for gluconeogenesis in the liver - Influences the secretion of appetite-regulating hormones Butyrate - Energy source for colonic epithelial cells - Promotes gut barrier integrity

Answer 33

- Immune mediated inflammatory disease - Affects the epithelium, lamina propria and other layers of the bowel wall. It can affect any part of the gut, but most commonly the terminal ileum / first part of colon - Can see non-caseating granuloma - Symptoms- abdo pain, fever, mouth ulcers, loss of appetite, fistulas - Genetic and environmental factors interact to produce disease. Potentially a role for an environmental trigger (e.g., infection with a pathogen; stress). Significant genetic associations with susceptibility and protection. NOD2. An intracellular PR involved in recognition of bacterial infection (specifically MDP). IL-23R. Th17-skewing cytokine receptor

Answer 34

1.Lack of factors essential for normal cell function o blood (ischaemia) o oxygen (ischaemia, hypoxia) o nutrients eg vitamin deficiencies o neural stimulation eg muscular dystrophies 2.Physical trauma, heat/cold 3.Chemical drug injury (prescription and recreational) -toxins eg alcohol metabolites 4. Inflammation- Autoimmune Inflammation 5. Metabolic and genetic disorders-eg. diabetes mellitus, obesity, glycogen storage disease

Answer 35

- deranged tissue/organ function - detection of leaked intracellular contents in blood (when severe membrane damage has occurred) - Morphological changes in the tissue - Light microscopic changes - Gross changes in surgical specimens/PM

Answer 36

**Apoptosis**- - Physiological process - Specific enzymes break down cells -Caspases - Neat and tidy Typically single cells - Cell suicide programme - Activated by some types of injury **Necrosis-** - Not physiological - Uncontrolled cell breakdown-non- specific enzyme activation - Messy process - Typically large groups of cells - Mass murder - Common pattern following injury

Answer 37

Coagulative- most common, less rapid shrinking of cells, tissue, structure transiently preserved but tissue weak and non- functional. Necrotic tissue- pale with yellow colour from acute inflammatory cells Liquifactive- rapid degradation of cells to liquid mass(mush)

Answer 38

- ECM in tact → return to normal - ECM damaged → repair and scar - Tissues that have no regenerative capacity repair and fibrous scarring

Answer 39

- Cell shrinks, cytoplasm stains darker - Chromatin condenses under the nuclear membrane and DNA fragmentation - Cell membrane blebs and then cell fragments in to membrane bound bodies - Apoptotic cell bodies express macrophage attractants and are phagocytosed by macrophages

Answer 40

**Reduced apoptosis-** Mutations in pro-apoptotic or anti- apoptotic proteins that allow cells with damaged DNA to survive eg in cancers, Mutations in Fas/FasL in autoimmune disorders **Increased apoptosis-** Seen in ischemic injury (MI, Stroke) where pathway is activated. Neurodegenerative diseases

Answer 41

**Closure by Primary Intention** Usually refers to deliberate closure of a wound that isn’t too large; edges of wound are aligned **Closure by Secondary Intention** Extensive tissue loss; no deliberate closure; ‘healing on its own’. Repair is prolonged, with formation of much granulation tissue **Tertiary Intention Healing** Intentional delay of wound closure – typically because of risk of infection, decontamination etc. Wound closure is performed after interventions and formation of granulation tissue

Answer 42

- At the time of trauma, vascular injury occurs on a microvascular -/+ macrovascular scale - The immediate response of the body is to prevent exsanguination -> promote haemostasis - Damaged arteries rapidly constrict through the contraction of smooth muscle triggered by SNS and vasoconstrictors released locally –thromboxane A2 and endothelin - Vessels up to a diameter of 5 mm can be completely closed through contraction, although this can only occur if the injury is in a transverse plane - In a few minutes, the reduced blood flow mediated by artery and arteriole constriction leads to tissue hypoxia and acidosis which promotes the production of vasoactive metabolites e.g., nitric oxide and adenosine which cause vasodilatation and relaxation of the arterial vessels. At this point coagulation is needed for haemostasis

Answer 43

- Mast cells degranulate releasing histamine - Increases vasodilatation and increases vascular permeability - Entry of inflammatory cells into the wound - Complement is activated - Neutrophils infiltrate the wound within an hour of the insult and migrate over the first 48 hours - Neutrophils carry out phagocytosis, degranulation and NETosis

Answer 44

- Macrophages are pro-inflammatory in the first days of wound healing (M1 phenotype) and become anti-inflammatory / more pro-resolution in later stages (M2) - Lymphocytes appear in the wound (~72 hours +) and are involved in regulation of wound healing (as well as adaptive response to infection). Persist until wound healed - Dendritic Epidermal T Cells (γδ T-cells) secrete keratinocyte growth factor (stimulates keratinocytes to proliferate) and IGF-1 (differentiation). Non-conventional T cell - Products of arachidonic acid metabolism have anti-inflammatory properties which dampen the immune response and allow the next phase of wound healing to arise

Answer 45

Angiogenesis Formation of granulation tissue Fibroblast migration Collagen deposition Epithelialisation Wound contraction

Answer 46

Initially the centre of the wound is avascular and relies on diffusion of oxygen and nutrients from the undamaged capillaries at the wound edge. Later a rich vascular network of capillaries is formed throughout the wound from offshoots of healthy vessels. Angiogenesis is triggered from the moment the haemostatic plug has formed: platelets release VEGF as well as TGF-β, PDGF and FGF. Hypoxia is a key driver. VEGF is secreted by macrophages, fibroblasts and other cells, stimulating endothelial cells to proliferate and migrate forming tubes. MMPs are important for remodelling of the ECM.

Answer 47

Initially the capillaries are fragile and permeable and contribute to tissue oedema and the appearance of healing granulation tissue. The resulting pink, vascular, fibrous tissue which replaces the clot at the site of a wound is termed granulation tissue.

Answer 48

By the third day, the wound becomes rich in fibroblasts which proliferate and migrate in response to growth factors (FGF, PDGF, also TGF-b). They lay down extracellular matrix proteins (collagen, fibronectins and proteoglycans) – TGF-b very important for stimulation of this. Fibroblasts release MMPs: collagenases MMPs 1, 8 and 13. Collagens synthesised by fibroblasts are the key component in providing strength to tissues. The resulting pink, vascular, fibrous tissue which replaces the clot at the site of a wound is termed granulation tissue. Once sufficient matrix has been laid down, fibroblasts change to a myofibroblast phenotype and become more spindle-shaped. They connect to the surrounding cells and ECM proteins (e.g., fibronectin and collagen)

Answer 49

In wounds closed by primary intention, collagen deposition is maximal by day 5 and this can often be palpated beneath the skin as a wound ridge. When a wound ridge is not palpable, this is an indication that the wound is at risk of dehiscence (re-opening). Overproduction of collagen can lead to the development of a hypertrophic scar. Hypertrophic scars remain raised and erythematous but remain within the confines of the original wound. Keloid scars do not remain within the wound confines. Risks for development of scars include wound infections and wounds where there is excessive tension

Answer 50

n wounds that are primarily closed, this phase can be completed within 24 hours. Cytokines and growth factors at the wound site stimulate basal epithelial cells at the wound edge to migrate across the wound bed. They adhere to the deposited ECM. They then proliferate, differentiate and stratify to repopulate epithelial cell levels and complete wound repair. A process called epithelial-mesenchymal transition (EMT) allows epithelial cells to gain motility and travel across the wound surface. In wounds that heal by secondary intention, the area lacking epithelial cells can be large. The wound must contract significantly before epithelialisation can be completed. In some cases this might never occur - skin grafting might be appropriate

Answer 51

Wounds begin to contract about ~ 7 days after injury. Mediated mainly by myofibroblasts. Cell bodies are pulled closer together decreasing the area of tissue needing to heal. This is influenced by wound shape, with linear wounds contracting fastest and circular wounds the slowest. Disorders of this phase of healing can lead to deformity and the formation of contractures

Answer 52

- Involves a balance between synthesis and degradation of collagen and other proteins which become increasingly well organised. - Wounds never achieve the same level of tissue strength - Normal epithelium & maturation of scar tissue - As the scar matures, the level of vascularity decreases and the scar changes from red to pink to grey with time - Factors influencing scarring outcome: type of wound, wound size, wound location

Answer 53

Haemostasis- haematoma forms, stabilises fracture; matrix for cells infiltrating; source of signalling molecules to initiate inflammation, coagulates in between and around the broken ends of the bone Inflammation- vasodilation and increased vascular permeability, influx of inflammatory cells, removal of debris, formation of granulation tissue (blood vessels, fibroblasts and new ECM), osteoprogenitor cells are recruited to the site (mesenchymal cells) Proliferation- soft callus (cartilaginous and bridges fracture ends) formation, chondrocytes lay down cartilage, capillaries connect to callus, after time soft callus is resorbed and replaced by hard callus (woven bone), cartilage matrix is progressively calcified and reabsorbed and replaced by bone, more mechanically rigid Maturation/ remodelling- woven bone is resorbed by osteoclasts and remodelled into lamellar bone by osteoblast deposition, mechanical stress is important

Answer 54

- A hypersensitivity reaction is an overreaction to a harmless substance(s) which results in an immune response that causes inflammation and tissue damage. - The many hypersensitivities can be classified into four groups, I to IV. - All hypersensitivities involve components of the adaptive immune system.

Answer 55

IgE - allergic rhinitis - allergic asthma - eczema

Answer 56

IgG - drug allergies - chronic urticaria

Answer 57

IgG - serum sickness - arthus reaction

Answer 58

Cell mediated - allergic contact dermatitis (+ to poison ivy) - chronic asthma - chronic rhinitis - graft rejection

Answer 59

-**Mast cells**- are tissue resident cells found predominantly in mucosal tissues near body surfaces and in connective tissues near blood vessels. IgE becomes bound to FcεRI (a type of Fc receptor) on mast cells. One mast cell can have on its surface pre-bound IgE antibodies covering a range of specificities. When the bound IgE is cross-linked, mast cells release histamine and other mediators (prostaglandins, leukotrienes, cytokines and enzymes) - **Eosinophils-** present in small numbers in the blood. Resident in connective tissues under mucosal surfaces. Like mast cells, eosinophils have receptors for IgE on their surface. Contain pre-formed toxic mediators (e.g., MBP and ECP) in granules, which they release on receptor crosslinking. They can also secrete cytokines. Th2 cells regulate the eosinophil arm of the immune response: • secrete cytokines (e.g., IL-5) that promote development and survival of eosinophils. • promote recruitment of eosinophils to sites of inflammation by stimulating release of chemokines (e.g., eotaxin) by activated endothelial and epithelial cells. - **Basophils-** a minor population in peripheral blood and not usually found in large numbers in peripheral tissues. Recruited to sites of inflammation, and activated in several ways: by PAMPs, cytokines and lipid mediators and … also by IgE. They bear FcεRI and degranulate on receptor crosslinking. Release histamine amongst other mediators. Cytokine production by basophils (specifically early secretion of IL-4 and IL-13) may be important in the initiation of Th2 responses

Answer 60

First exposure is asymptomatic

Answer 61

- Most multicellular parasites infect through skin and mucosal tissues. - These tissues are predisposed to developing Th2 responses. - Parasitic worms can use proteases to access the body. - We respond to several proteases as allergens e.g., Der p 1 in faeces of house dust mites. - Many allergens are soluble in the mucosa and present at low doses. Low antigen doses favour Th2 over Th1. - Parasites often need to be expelled by muscle contraction and enzymatic breakdown

Answer 62

**tendency to develop allergic diseases** - In Caucasian populations of Europe and North America, up to 40% of people are atopic. - Atopic individuals have higher levels of IgE and eosinophils in their blood. - Strong genetic component to risk – polymorphisms of multiple genes including on chromosomes 5, 6 and 11 - **MHC II** – Enhanced presentation of allergen peptides - **IL-4R** – Increased signaling from IL-4 - **IL-4** – Variation in IL-4 expression - **FcεRI** – IgE binding - On chromosome 5, there is a cluster of cytokine genes (including IL-3,-4,-5 and -13) which are all involved in regulating components of the allergic immune response

Answer 63

Similar to Type II except antibodies bind to soluble antigen (not attached to cells)

Answer 64

**Type IVa** Classic Th1 immune reaction where sensitised T cells will secrete IFN-γ and TNF-⍺ leading to macrophage activation. Th1 cells can also act as co-stimulators for CD8 T cell responses as seen in Type IVc **Type IVb** Driven by Th2 cells which will secrete IL4, 5 and 13 to promote B cell production of IgE and IgG4. IL5 enhances eosinophil activation, degranulation and cytotoxicity Chronic asthma is a Type IVb reaction which results in the activation of eosinophils. Upon activation, eosinophils will degranulate and cause further inflammation and recruitment of additional inflammatory cells resulting in chronic inflammation of the airways. **Type IVc** CD8 T cells function as the effector cells and cause direct damage through perforin, granzyme and Fas-ligand dependent mechanisms. Often occurs with other Type IV reactions **Type IVd** T cells activate sterile neutrophilic inflammation. CXCL8/GM-CSF producing T cells are activated by antigen. These recruit neutrophils via CXCL8 and promote survival through GM-CSF which will then create a neutrophil rich environment.

Answer 65

This is a type 1 hypersensitivity to a foreign but harmless antigen. There is no autoimmune component. IgE mediated crosslinking of FceRI causes mast cells to become activated and degranulate, releasing histamine(preformed) and leukotrienes (synthesised de novo) – causing smooth muscle contraction and increased vascularpermeability. Histamine can activate nerve endings directly to cause itching. Eosinophils may be recruited to the tissue and can accumulate in chronic disease. They release mediators such asMBP which are very damagingBasophils have an important role in systemic anaphylaxis, which can occur in this condition. Th2 cell infiltrate in the tissue characteristic of chronic allergy. They release cytokines including IL-4, IL-5 and IL-13

Answer 66

Itching, Swelling, Airway constriction, Pulse and blood pressure changes (in anaphylaxis, systemic vasodilation and increased vascular permeability can causehypovolemic shock)

Answer 67

autoimmunity Failure of central and/ or peripheral self-tolerance mechanisms mean that an antibody response is mounted to self antigens at the postsynaptic terminal of the neuromuscular junction Plasma cells secrete IgG antibodies (mostly IgG1, but also IgG3 and other types) which bind to the nicotinic acetylcholine receptor. There are other autoantigens, including MuSK and LRP4 Antibody binding can lead to various effects: internalisation and degradation of the receptors; direct blockage of ACh binding; and activation of complement which damages the postsynaptic membrane The consequence is impairment of signalling required to trigger muscle contraction. This may be manifested in ptosis(extraocular muscles; less severe) or difficulty breathing (diaphragm and other respiratory muscles; more severe)

Answer 68

Diagnosis of the condition involves looking at the clinical picture (muscle weakness, commonly ocular initially) and thenperforming antibody tests (specificity and titre). There is a minor subgroup of seronegative MGPyridostigmine (oral treatment) is an anticholinesterase. By inhibiting the breakdown of acetylcholine, is increases theamount of it available to signal at the NMJ. It is used for symptomatic controlPrednisolone is a glucocorticoid immunosuppressant. Low dose treatment produces a significant clinical response inmost patients with mild to moderate disease. It ultimately suppresses the immune response, reducing autoantibodyproduction and consequently muscle degenerationIntravenous immunoglobulins (IVIg) neutralises the autoreactive antibodies (preventing them from binding their target)and also neutralises cytokines and blocks activating Fc receptors. It is used in the situation of a severe acuteexacerbation of myasthenia gravis

Answer 69

For diagnosis, muscle weakness particularly with repetitive use. Ocular muscles often involved with th consequences of doubledivision (diplopia) and droopy eyelids (ptosis). Muscles in face, limbs and trunk can be involvedRespiratory distress is indicative of myasthenic crisis and is a potentially life threatening exacerbation

Answer 70

This is a type 3 hypersensitivity (sometimes also manifesting as type 2) to self antigens. It is an autoimmunityFailure of central and/ or peripheral self-tolerance mechanisms mean that an antibody response is mounted to selfantigens normally found in the cell nucleus – for example dsDNA, histones, and ribonucleoproteinsPlasma cells secrete IgG antibodies (IgG1, G2 and G3 may all be present) which bind for example to dsDNAreleased from dying/dead cells. This leads to formation of immune complexes (antigen, antibody, complement)which can deposit in vasculature.Several different organs can be damaged: lupus nephritis progressing to end stage kidney disease; jointinflammation progressing to erosive arthritis; and pleuritis and pericarditis affecting the lung and heart

Answer 71

Diagnosis is based on the clinical picture (skin, joint, kidney, serosa) and the presence of anti-nuclear antibodies (usually anti dsDNA is present) Corticosteroids are immunosuppressives. They suppress the adaptive immune response and also reduce the inflammation and tissue injury consequent to immune complex deposition (activation of complement; tissue damage by myeloid cells and so on Belimumab is a monoclonal antibody therapy which blocks (binds and neutralises) the B cell survival and stimulatory factor BAFF/BLyS. It causes B cell apoptosis and reduces autoantibody levels

Answer 72

Wide ranging symptoms but rash on the face, and arthritis, are classic presentations The arthritis in the case will have been an early manifestation of SLE. This disease perhaps should have been diagnosed sooner

Answer 73

This is a type 4 hypersensitivity (driven by T cells). It is not autoimmune as the immune response is against harmless alloantigens. Those antigens are from the donor and are therefore foreign to the recipient Direct allorecognition is central to acute rejection. Donor APC that are carried with the donor organ present allo MHC directly to the recipient T cells. Allo MHC I will activate cytotoxic CD8 T cells, which will then damage the graft. Allo MHC II will activate helper CD4 T cells, which assist the cytotoxic T cell response and also secrete inflammatory cytokines In indirect recognition, recipient APC phagocytose, process, and present donor antigens to T cells. This is slower, but can result in cytotoxic T cell, helper T cell and also T-dependent antibody responses against the graft

Answer 74

The patient has been on a triple immunosuppressant regime since transplantation to prevent organ rejection: Tacrolimus is a calcineurin inhibitor and inhibits the activation of T cells Mycophenolate mofetil inhibits the synthesis of guanosine monophosphate and therefore inhibits cell proliferation Prednisolone is a corticosteroid and suppresses inflammation and immunity Bronchoscopy + biopsy or bronchiolar lavage would be performed to look for immune cell infiltration into the graft - and to look for signs of infection. This will help discriminate infection from rejection. Impaired immunity in a patient under immunosuppression results in a much higher risk of serious infection

Answer 75

Reduced organ function, pain at the site Systemic symptoms of inflammation: fever and flu like symptoms

Answer 76

Key to identify the allergen in order to know what to avoid. In this case the Ara peanut allergens are the most likely.These may also be present in other foods. Adrenaline given. It binds adrenergic receptors – critically here the b2 receptors on bronchial smooth muscle,causing bronchodilation and preventing asphyxia. Chlorphenamine is an H1 histamine receptor antagonist administered subcutaneously, intramuscularly or intravenously (relief from swelling and itching). Hydrocortisone is a corticosteroid which suppresses the inflammatory response. It is given to reduce inflammation inthe late phase and reduce the chance of a subsequent severe reaction (e.g., anaphylaxis)