Hypersensitivity disorders II

Question 1

which of the following symptoms of anaphylaxis is the most life threatening?

Answer 1

vascular permeability (drops blood pressure, and organs don’t receive oxygenated blood)

Question 2

Hygiene hypothesis

Answer 2

explains why western nations have such a high rate of hypersensitivity
- too clean
- reduces exposure to pathogens (from animals and such)
- vaccination
- overreliance on antibiotics (reduced the educaiton of the immune system)

outcome:
- development of the immune system is held bacl
- develops an immune system that is incapable of fighting off “real world infections”.

Question 3

basophils

Answer 3

• key cell initiating Th2 response
• make IL4 and IL13 , at the start of the immune response
• can drive isotype switching to IgE and IgG4 through interaction with B cells through their CD40L

They can kind of act like a T cell in this way

Question 4

lipid mediators

Answer 4

prostaglandins and leukotrienes

These are targeted in treatment of allergies and inflammation

Question 5

Type II Allergic Rxn

Answer 5

Antibody induced

• cell or matrix associated antigen
• complement, FcR+ cells (phagocytes, NK cells)
• Some drug allergies (ex: penicillin)

IgG driven

Question 6

Type III

Answer 6

Antibody induced
IgG driven
- soluble antigen
- complement phagocytes
- serum sickness, Arthus reaction

Question 7

Type IV hypersensitivity

Answer 7

Th1 driven, T cell induced
- soluble antigen
- macrophage activation
- contact dermatitis, tuberculin reaction

Question 8

Type II mechanism

Answer 8

existing structures, generating an anitbody response

Question 9

Type III mechanism

Answer 9

serum coming from another individual, forms immune complexes.

Question 10

Type IV mechanism

Answer 10

• T cell expansion and Th1 response with macrophages and T cells. Causes rash or swelling around the nickel containing jewelery

Question 11

Type II

Answer 11

Small molecules that bind to cell surface molecules, changing their structure. Perceived by the immune system as foreign.
- antibody response develops, IgG
- Upon Ab binding altered molecules on cells, leads to their destruction by complement and phagocytosis
- Penicillin is one molecule that can induce this activity

Question 12

Penicllin structure

Answer 12

Has a reactive bond, that is able to focus on a bacterial transpeptidase or localize on an erythrocyte.

• Binds to bacterial transpeptidase and inactivates it OR
• Penicillin modifies proteins on human erythrocytes to create foreign epitopes.

Question 13

Penicillin - Protein conjugates

Answer 13

stimulate the production of anti-penicillin antibodies
- complement coated penicillin modifed erythrocytes are phagocytosed by macrophages
- Macrophages present peptides from penicillin-protein conjugate and activate specific CD4 T cells to become Th2 cells.
- B cells are activated by antigen and by help from activated Th2 cells
- plasma cells secrete penicillin specific IgE which arms mast cells. IgG is also produced
- Penicillin modified erythrocytes activate armed mast cells causing anaphylaxis.

Question 14

Blood group antigens and transfusions

Answer 14

• Transfusion can give rise to a life threatening Type II hypersensititvity response
• the major immunogenetic barrier to transfusion is the structural polymorphisms of the carbohydrates decorating the erythrocyte surface
• The antigenic difference in these molecules are reffered to as the ABO system of blood group antigens.

Question 15

A antigen

Answer 15

has a GalNAc on its terminal residue

Question 16

B antigen has

Answer 16

terminal residue of Gal (galactose)

Question 17

O antigen

Answer 17

absence of terminal residue

Question 18

why do we produce antibodies against other people’s blood group antigens?

Answer 18

because blood group antigens are very similar to those expressed by many bacteria and we only develop tolerance to those our RBCs express

Question 19

which blood type is the universal donor?

Answer 19

Blood group O

Question 19

which blood type is the universal donor?

Answer 19

Blood group O

Question 20

what blood group can recieve blood from any group?

Answer 20

AB

Question 21

AB blood can only be transfused safely into another

Answer 21

AB patient

Question 22

Type III hypersensitivity

Answer 22

Initiated by immune complexes (antigen-antibody complexes) depositing on the walls of small blood vessels or alveoli
- immune complexes activate complement
- inflammation and tissue damage follow complement deposition
- can be a side effect of therapeutic treatment with Ab or other proteins from non-human animal species

• Arthus reaction or serum sickness

Question 23

Mediated tissue injury - immune complex

Answer 23

site of immune complexes -> complement and Fc receptor - mediated recruitment and activation of inflammatory cells

leads to recruitment of neutrophils and lysosomal enzymes and ROS

all leads to

Vasculitis (inflammation of vasculature)
- shows up as hemmorrhage in the skin and uricarial rash (both result from serum sickness)

Question 24

vasculitis

Answer 24

blood vessel walls

Question 25

nephritis

Answer 25

renal glomeruli

Question 26

arthitis

Answer 26

joint spaces

Question 27

Arthus reaction

Answer 27

perivascular area

Question 28

Farmer's lung

Answer 28

Alveolar/capillary interface

Question 29

immune complexes

Answer 29

- can be small or large - their size, depends on the concentration of antigen and antibodies

Question 30

small complex

Answer 30

little antibody, excess antigens **Early response**

Question 31

large immune complexes

Answer 31

equal amount of antigens and antibodies potenitally very damaging **Middle of immune response**

Question 32

medium sized immune complex

Answer 32

excess antibody, little antigen **late in immune response**

Question 33

type IV hypersensitivity

Answer 33

caused by the products of antigen specific T cells - CD4+ Th1 mediate the majority of these responses, reactions to insect bites, tuberculin skin test - reffered to as **delay type hypersensitivity (DTH)** because it takes several days for symptoms to develop

Question 34

DTH proteins and local skin swelling

Answer 34

proteins - insect venom - mycobacterial proteins (tuberculin, lepromin) skin swelling - erythema - induration - cellular infiltrate - dermatitis

Question 35

contact hypersensitvity (type IV)

Answer 35

Haptens: - Pentadecacatechol (poison ivy) - DNFB Small metal ions - Nickel - Chromate Local epidermal reaction - Erythema - cellular infiltrate - Vesicles - intraepidermal abscesses

Question 36

Gluten sensitive enteropathy (celiac disease)

Answer 36

Antigen - **Gliadin** Villous atrophy in small bowel - malabsorption

Question 36

Gluten sensitive enteropathy (celiac disease)

Answer 36

Antigen - **Gliadin** Villous atrophy in small bowel - malabsorption

Question 37

DTH reactions on the cellular level

Answer 37

Mediated by antigen-specific **effector T cells** Manifested as local irritation that occurs 24-72 hours after exposure - Antigen is injected into subcutaneous tissue and processed by local antigen presenting cells - Th1 effector cell recognizes antigen and releases cytokines which act on vascular endothelium - Recruitment of phagocytes and plasma to site of antigen injection causes visible lesion

Question 38

granulomas

Answer 38

chronic DTH response Occurs in lungs and lymph nodes of those infected with **mycobacterium**. Provides a mechansm for walling off the infection from the rest of the bosy. Sometimes have a caseous or necrotic center. activated macrophages and T cells. walled off by fibroblasts - contains the infection. kept in a latent state until there is some sort of stress or activation.

Question 39

Th1 is the driving factor of a Type IV rxn

Answer 39

produces IFNy - activates macrophages, increasing release of inflammatory mediators

Question 40

the pathogenesis of celiac disease

Answer 40

inflammation of the small intestine is caused by CD4+T cells, responding to peptides derived from gluten. 1. gluten degraded in the gut lumen to give resistant fragment 2. gluten fragment enters gut tissue and is deaminated by transglutaminase 3. Naive CD4 T cell responds to deaminated peptides presented by HLA-DQ 4. Inflammatory effector T cells cause **villous atrophy**