Immune System Gone Wrong

hypersensitivities

reactions of the adaptive immune response that result in host damage or death

1. antibody mediated/immediate response is also known as allergy or allergic rxn/response (happens via IgE or IgG binding & onset is minutes-hours)

2. cell mediated or delayed-type hypersensitivity (Th1 cell recruitment & activation of macrophages; onset time is days)

antibody mediated hypersensitivity response

• immediate → onset is minutes-hours

• allergy or allergic rxn/response

• happens via IgE r IgG binding

cell mediated hypersensitivity

• aka delayed-type (DTH)

• Th1 cell recruitment

• activation of macrophages

• onset time = days

describe allergy process

1. allergen bound by B cell

2. allergen processed & presented to Th2 cell

3. Th2 cell provides B cell help

4. B cell forms plasma cells

5. plasma cell produces IgE

6. IgE sensitizes tissue mast cells by binding to surface IgE receptors

7. subsequent exposure to antigen

8. antigen cross-links 2 antibody molc.

9. release of allergic mediators (histamines, serotonin)

Type I hypersensitivity

• immediate

• IgE sensitization of mast cells (antibody mediated)

• latency = minutes

• ex. rxn to bee sting, hay fever

type II hypersensitivity

• cytotoxic

• IgG interaction with cell surface antigen (antibody mediated)

• latency = hours

• ex. drug rxns (penicillin)

type III hypersensitivities

• immune complex

• IgG interaction with soluble or circulating antigen (antibody mediated)

• latency = hours

• ex. systemic lupus

type IV hypersensitivity

• delayed type

• Th1 inflammatory cell activation of macrophages (Tcell mediated)

• latency = 24-48 hrs

• ex. poison ivy, TB test

examples of environmental allergens

• molds

• pollen

• pets/dander

• dust mites

what determines the mechanism of allergy?

1. type of antigen

2. site of exposure (GI/airway)

3. Th2 cells (signal B cells to produce IgE antibodies)

describe mechanism of allergy

• IgE binds IgE receptors on mast cells or basophils to a lesser extent & causes large amounts of histamine & serotonin to be released

• mast cells are normally found & bound to the epithelium/endothelial lining → when degranulation occurs, histamine & serotonin flood lumen of the gut or travel thru bloodstream/airways, triggering potential anaphylatic response

effects of serotonin & histamine

• vasodilation (widening of blood vessels, drop in BP)

• smooth muscle cell constriction (harder to breathe)

where is most (~95%) of serotonin made?

gut

where are mast cells commonly found?

• epithelium

• endothelial lining

what is used for less serious rxns such as environmental allergies?

antihistamines, esp. 1st generation ones like benadryl

what is used for anaphylactic responses?

epinephrine

epinephrine

counteracts effects of histamine & serotonin, constricting blood vessels & relaxing smooth muscle

• used for anaphylactic responses

desensitization

repeated exposure to allergen in increasing doses to try to shift the class of antibody from IgE to IgG or IgA

• generally still have allergic response but threat of dying is removed

• how peanuts moved from 1st to 4th biggest allergy

allergies are often _________

hereditary

Xolair

• new type of drug given 1x montly to help bind IgE and prevent it from binding to IgE receptors on mast cells

• can be harmful if the person contracts another infection that would need IgE

delayed type hypersensitivity is a result of ____ cell being activated in resposne to an antigen that hasn’t been seen before

Th1

when things like toxins, chemicals, etc. contact our skin, they can ________ or ________ proteins, which Th1 cells & APCs will recognize as _______ (_________) and cause this type of immune rxn

bind / destroy / antigens / (DAMPs)

which allergy metod is used to determine TB infection?

delayed type hypersensitivity

• check 48 hrs after exposure

what happens when the adaptive immune (negative selection) response fails?

T cells and B cells can mount a response against host cells

some conditions can be treated by supplying ________ of the thing being attacked

excess

• ex. insulin & thyroid hormones

multi-organ/site responses often require the use of ______________ or __________ drugs, increasing the risk of alter infections from opportunistic pathogens

anti-inflammatory / immunosuppressive

effects of treating multi-organ/site responses w/ anti-inflammatory and immunosuppressive drugs

increases risk of later infection from opportunistic pathogens

normally a given TCR and MHC-I/II molc have specificity for _________

1 antigen

superantigens bind outside of ____________

classical binding grooves

steps leading to cytokine storm

1. superantigens bind outside of classical binding grooves

2. activate 225% or more of all T cells

3. subsequently activate B cells

4. cytokine release

result of cytokine storm is similar to ________ given this large immune activation

septic shock

primary immunodeficiencies

• usually something born with or developed early on in life

• affects a subset of innate, adaptive, or both

• can be fatal

Severe Combined Immunodeficiency (SCID)

defect in bone marrow that fails to produce lymphocytes

CVID

fails to produce plasma cells → low levels of antibodies produces

X-linked disorders primarily occur in _________

males

secondary immunodeficiencies

• acquired after an infection/disease/illness

• most studied ex. is HIV

what type of immunodeficiency is HIV?

secondary

most vaccines are built around activating _____________ of the immune system

both arms (adaptive & innate)

TCRs and BCRs only recognize ________-derived antigens

protein

why are capsule polysaccharides a problem?

TCRs and BCRs only recognize protein-derived antigens

how do vaccines get around the capsule polysaccharide problem?

vaccines can be conjugated to other protein antigens to recruit cells from adaptive response

• ex. pneumococcal vaccine uses diptheria toxin to link the immune system (trick immune system into working)

what antibody classes would be made in giardia? (GI parasite)

• IgE

• IgM

• IgA

what pathogen recognition receptors (PRRs) are activated in giardia (GI parasite)?

none- parasites tend to run undetected in the body

• if any were activated, it could be TLR-1, 2, 6

whic innate cells would be activated in giardia?

• NK cells

• eosinophils

which adaptive cell types would be activated in giardia & where?

CD4, activated in MALT (closest secondary lymphoid organ)

how could we treat primary immunodeficiencies?

bone marrow transplant

how could we treat secondary immunodeficiencies?

• immunosuppressants (anti-TNF-a)

• treat malnutrition (with food)

• clear infection

is it good to prevent all allergies and hypersensitivities?

no— we would lose the ability to respond to threats