immunology unit 3

layers of mucosal barrier

lumen, outer/inner mucus layer, epithelial cells

IgA in mucosal barrier

found in inner mucus layer, 2-4 grams secreted into lumen everyday via endocytosis.

can neutralize pathogens/toxins and transport Ag across epithelium

goblet cell

produces mucus

paneth cell

produces antimicrobial peptides

why do we tolerate commensals?

1. nutrition

2. protection

3. pivotal for immunologic development

role of commensal tolerance in nutrition

microbes break down complicated chemical structures into things we can utilize

role of commensal tolerance in protection

colonization of mucosal surfaces with commensals takes up space

• when you take antibiotics, it removes the healthy commensals and opens you up to infection (C Diff)

role of commensal tolerance in immunologic development

germfree mice: less Ig, Treg, TH1, TH17, more allergy

antibiotics in early life linked to: allergy, atopic dermatitis, asthma, allergic rhinitis

how do epithelial cells know what is a pathogen and what is a commensal?

different TLR expression patterns

apical- in gut

basolateral- in body

M cells

moves things from lumen into the basolateral small intestine

MALT

mucosa-associated lymphoid tissues

NALT

nasopharygeal-associated lymphoid tissue

• salivary glands

• tonsils

GALT

gut-associated lymphoid tissue

• Peyer’s Patches

• Mesenteric lymph nodes

• appendix

• cryptopatches and isolated lymphoid follicles

BALT

bronchus-associated lymphoid tissue

TALT

tear duct associated lymphoid tissue

how does IgA enter the gut?

activated B cells in Peyer’s Patches secrete IgA antibodies

type I hypersensitivity

occurs when IgE gets stuck to degranulating mast cells after crosslinking, known as a classic allergy

type II hypersensitivity

non-IgE antibodies induce cell death through phagocytosis, complement, or ADCC.

ex: ABO mismatch in blood

type III hypersensivity

immune complexes are formed and circulated through blood.

ex: autoimmune diseases

type IV hypersensitivity

delayed hypersensitivity where a T-cell response occurs.

ex: nickel allergy

sensitization stage of allergy development

initial adaptive immune response against an allergen

pentadecatechol

causative agent of poison ivy- hapten

what triggers anaphylaxis?

mast cells

specialized epithelial cells of mucosa

goblet, paneth, m cell

histocompatibility

measure of antigen similarity between host and donor

hemolytic disease of the newborn

an antibody response in an Rh- mother against a Rh+ baby

cytotoxic

hyper-acute rejection

why does hemolytic disease affect 2nd child?

mother becomes sensitized against Rh antigen during first childbirth

autograft

transplant from self

allograft

transplant from the same species

isograft

transplant from identical twin

xenograft

transplant from another species

lupus butterfly rash

type III hypersensitivity, immune complexes occlude in thin blood vessels in the nose and cheeks, causing inflammation.

how do antigens cross the lumen?

• via transcytosis by M cells

• moved by macrophages

direct recognition

host t-cell recognizes donor MHC molecule loaded with host antigens

indirect recognition

host t-cell recognizes host MHC molecule loaded with donor antigen peptides

peanut study

UK kids have way higher peanut allergy percentages than Israeli kids- peanut snack

PRRs in GI tract

much less in colon than small intestine because of commensals. We don’t want to kill our good gut bacteria that absorbs nutrients and kills off dangerous pathogens.

hyper-acute rejection

occurs days-weeks after transplant. pre-existing recipient antibodies attack donor antigens.

ex: mismatched blood types

acute rejection

weeks-months, body doesn’t recognize the donor’s tissue/organ, so immune response is triggered.

chronic rejection

months-years. this accounts for damage from responses against alloantigens over time

GVHD

graft-versus-host disease

donor T cells attack host tissue

hyper-acute rejection

oral tolerance

our bodies become tolerant of antigens, such as food proteins, which prevent any immune response.