Immuno

Question 1

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

Answer 1

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.

Question 2

Urticaria pathogenesis and presentation

Answer 2

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

Question 3

pathogenesis of hereditary angioneurotic edema

Answer 3

cause is genetic by AD transmission → C1 inhibitor deficiency → classical complement pathway has “no breaks” → excess secretion of bradykinin (mediator of edema)

Question 4

what is the specific immunological mediator of edema

Answer 4

bradykinin

mn: Brady sounds like Brody which sounds like the name of a swol football player

Question 5

Stevens-Johnson Syndrome and toxic epidermal necrolysis are both variants of which type of skin disorder

Answer 5

Erythema Multiforme (an acute inflammatory dermatosis)

Question 6

what are the types of immunce cells present in the epidermis versus the dermis

Answer 6

• 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

Question 7

What are the GENERAL descriptions of the 4 types of hypersensitivity responses?

Answer 7

Question 8

what is the hallmark of type I reaction

Answer 8

degranulation of mast cells

Question 9

what type of hypersensitivity reaction is shown

Answer 9

Type 1

Question 10

what type of hypersensitivity reaction is shown

Answer 10

Type II

Question 11

_________is a marker of mast cell degranulation

Answer 11

tryptase

Question 12

____and _______antibodies induce hypersensitive reactions
by activating complement.

Answer 12

IgG and IgM antibodies, induce hypersensitive reactions
by activating complement.

Question 13

what two types of antigens most commonly initiate a Type II hypersensitivity reaction

Answer 13

1. self
2. drug

Question 14

Which hypersensitivity reactions present within 1-3 hours of exposure to antigen?

Answer 14

Types II and III

Question 15

What are the type(s) of immune cells that are responsible for Type III HSRs

Answer 15

Helper T cells and Cytotoxic T cells

Question 16

• 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

Answer 16

Type III

Question 17

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.

Answer 17

asthma

Question 18

what is the characteristic presentation of an atopic dermatitis rash.

Answer 18

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.

Question 19

In _________ (which HSR) reactions, antigen-antibody complexes deposit in healthy tissues, initiating localized inflammatory responses in these tissues.

Answer 19

Type III

Question 20

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.

Answer 20

Type IV

Examples of type IV hypersensitivity reactions include type I diabetes mellitus, multiple sclerosis, and Hashimoto’s thyroiditis.

Question 21

Name an environmental risk factor for lupus

Answer 21

Question 22

Type I diabetes mellitus, multiple sclerosis, and Hashimoto’s thyroiditis are all examples of which hypersensitivity reactrion

Answer 22

Type IV

Question 23

idiopathic thrombocytopenic purpura is caused by what type of antibodies

Answer 23

anti-platelet antibodies

Question 24

Antibodies against neutrophil proteinase 3 are also called ____

Answer 24

(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.

Question 25

Polyneuropathy and melena - what small/medium size vasculitis could be the cause

Answer 25

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.

Question 26

what is this

Answer 26

p-ANCA staining

Question 27

what immune system element mediates opsonification of bacteria and immune complexes

Answer 27

C3 –> C3b

Question 28

terminal complement deficiency leads to what specific breakdown in immune response

Answer 28

Deficiency of factors C5-9 (terminal)–> Defective formation of the membrane attack complex (pokes holes in cells) –> susceptibility to Neisseria

Question 29

what is the immune response in intracellular pathogens

Answer 29

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

1. cytosolic intracellular pathogen –> MHC I presentation
2. phagosomal intracellular pathogen (e.g. TB)–> MHC II presentation

Question 30

what is the type III HSR

Answer 30

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.

Question 31

what is the type 1 HSR

Answer 31

IgE-mediated mast cell activation is the mechanism underlying type I hypersensitivity reactions (including anaphylaxis)

Question 32

t/f Viruses do not cause hypersensitivity reactions

Answer 32

TRUE

Question 33

in what places of the thymus do negative and positive selection occur

Answer 33

negative selection occurs in the medulla

positive selection occurs in the cortex

Question 34

AIRE gene product mediates __________

Answer 34

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).

Question 35

where does V(D)J recombination of B cell immunoglobulin heavy chain gene segments occur

Answer 35

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.

Question 36

what is the MOST important immune factor in the formation of granulomas

Answer 36

IFN-gamma bevause it activates macrophages which are critical for granuloma formation

Question 37

Pathogenesis of Hyper IgE syndrome (aka Job syndrome)

Answer 37

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

Question 38

IgM’s main function is to ________________________

Answer 38

initiate the complement system

Question 39

T cell–independent method of B cell activation is utilized in what immune response

Question 40

eosinophila can be caused by:

(mn: PACMAN Eats)

Answer 40

• Parasites
• Asthma
• Chronic Adrenal Insufficiency
• Myeloproliferative disorders
• Allergy (Type 1 HSR)
• Neoplasia (Hodkins lymphoma)
• Eosinophilic granulomatosis with polyangiitis

also MI after 12-24 hours

Question 41

pathophysiology of allergic contact dermatitis

Answer 41

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

Question 42

function of IL-6

Answer 42

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)

Question 43

function of IL-8

Answer 43

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

Question 44

mechanism of H. Influenza B vaccine

Answer 44

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.

Question 45

pathogenesis of superantigen mediated T-cell activation

Answer 45

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)