exam 3

Layers of the mucosal barrier

-lumen

-outer mucus

-inner mucus

-epithelialOuter cells

Outer Mucus Layer

The thinner outside layer where commensal bacteria is located.

Inner Mucus Layer

Thick inner layer with antimicrobial proteins and IgA to keep distance of of bacteria and inside body.

Epithelial cells

Cells separating lumen and body

Types of epithelial cells

-Goblet

-Paneth

-Microfold cells

Goblet cells

secrete mucus

Paneth cells

create antimicrobial peptides

Where are mucosal sites

Urogenital tract, gastrointestinal tract, respiratory tract

Why do we tolerate commensal bacteria?

Nutrition, Protection, Immune maturity

Nutritional benefits of commensals

Microbes break down complicated chemical structures into forms we can use

Protection benefits of commensals

Take up space on surfaces and out-compete bad bacteria

Immunological development benefits of commensals

Exposure to “good” commensals early in life help to mature the immune system

Biggest rule of mucosal immunology

You must recognize non-self and self

Bug-centric view of immune system tolerating commensals

Bugs train us by instructing our immune system. Made the system become tolerant

Human Centric view of immune system tolerating commensals

Humans have evolved systems to not respond to commensals

How do epithelial cells know what is commensal

Different TLR expression patterns. More PRRs are on the basolateral side because bacteria on apical side is normal

Microfold (M) cells

Move things from the lumen to body side to get Ag into body

Ways to get Ag across mucosal barrier

-macrophages

-Goblet cells

-Dendritic cells

-IgA gets pulled back

Peyers patch

collection of lymph cells right under the M cells

Mesenteric lymph nodes

Gut drains the lymph to these

Distinguishing cytokine in Peyers patches

TGFB because T regs dampen reactions since you don’t want to react to everything you eat.

Homing receptors

Mucosal lymphocytes are trained to know to come back to mucosal sites for shared protection across sites.

Hypersensitivity

Immune reactions you don’t like

2 stages of hypersensitivity

sensitization and secondary exposure

Sensitization

first exposure to an allergen that results in production of Ag-specific IgE.

-Takes about 1 week to set up response

Secondary Exposure

Second exposure to allergen, Mast cells activated by IgE crosslinking lead to degranulation

-Takes minutes to hours to respond

Type 1 hypersensitivity pathway

Allergen gets into mucosa through skin, DC prime T-cells to TFH and activates B cells, Plasma cell produces allergen-specific IgE, upon exposure, IgE binds to mast for degranulation.

Type 1 is mediated by what Ab class

IgE

What cells and cytokines affect Type 1

TH2 response drives IgE production by the IL4 cytokine. Releases histamines and drives the influx of neutrophils and eosinophils

Atopy

Predisposition to type 1 hypersensitivity

-Causes high rates of asthma, allergy, and eczema

Type 1 is also known as:

Allergies or IgE Mediated Hypersensitivity

Type 2 is also known as:

Cytotoxic hypersensitivity

Effects of Type 2

Non-IgE Ab can induce cell killing through phagocytosis, ADCC, or complement

Type 2 is mediated by what Ab

non IgE

3 ways Type 2 Ab kill cells

-phagocytosis

-ADCC

-Complement

Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)

NK cells stick to Ab tagged cells to kill them

ABO Type 2 blood response

Mismatched blood reacts due to blood types have anti-A/B antibodies depending on blood type.

-Carbs on surface of RBC are Ag (TI-response)

Hemolytic Disease of Newborns

Moms who are RH- will become reactive during the second pregnancy due to blood mixing at birth and exposure to Rh

Rhesus (Rh)

proteins in blood

Type 3 is also known as:

Immune-Complex Mediated Hypersensitivity

Effects of type 3

Immune Complexes (ball of Ab and proteins) glob up in your body

Mediators of type 3 reaction

Antibodies, mast cells

Arthus reaction

Physical trauma to your blood vessels from globs that can’t go through. Bruise

Length of time for type 3 to occur

few hours

Lupus

Antibodies react to DNA in blood and for clumps that affect vessels and kidneys

Serum Sickness

Large injections of foreign antigens (horse serum for anti-venom) can trigger a reaction after repeated use

Length of time for type 1 to occur

minutes

length of time for type 2 to occur

many hours or 1-2 days

length of time for type 4 to occur

days to weeks

Type 4 is also called:

Delayed/T-cell Mediated Hypersensitivity

Mediators of type 4 reaction

T-cell mediated (no ab)

Effects of Type 4

T-cell response that you don’t want. Respond to a non-harmful Ag

Tuberculin Skin Test

Use a small amount of Tuberculin protein and inject under the skin. If you react you have been exposed to it because T-cells respond

Poison Ivy

First reaction takes days because T-cells respond to the oil on the leaves (HAPTEN)

Hapten

A substance that can alter proteins to make them antigenic and cause a T-cell to respond to something it normally wouldn’t

Hygiene Hypothesis

Immune system evolves with common pathogens at an early age. Lack of exposure to infectious agents at an early age increases risk of allergy in the future.

Results of the Amish study

Amish live closer to what early humans did and have more exposure to pathogens which strengthens their immune system by responding early in life and developing more TRegs to decrease allergy.

Why are peanuts common antigens?

They have proteins with carbs on outside that PRRs often recognize. They are also very heat stable after roasting and don’t break apart easy.

Oral tolerance

Training your immune system not to react to certain antigens by exposure.

Peanut study results

Infants who consumed peanuts at a young age were less likely to develop allergies later. Peanut dust is everywhere so when it gets through the skin you can develop a reaction to it.

Peter Medawar Experiment results

Every organ you transplant has immune cells so the body needs to learn to communicate.

autograft

self to self transplant

Isograft

identical twin transplant

allograft

non-genetically identical transplant

xenograft

one species to another transplant

alloantigen

different version of self-proteins within members of same species (MHC shape)

histocompatibility

measure of tissue compatibility based on antigenic similarity

Hyper-acute rejection

Pre-existing antibodies react against blood antigens and cause vessel death

-immediate

Acute rejection

T-cells react against self-Ag that look different between donor and recipient. Occurs in all allografts

-days to weeks after

Direct recognition

Self T-cells recognize foreign MHC on donor APCs and react

Indirect recognition

Self T-cells recognize donor peptides in self MHCs and APCs

Chronic rejection

Same mechanism as acute but after time scar tissue builds up and damage accumulates causing organ death

-months to years later

Graft versus host disease (GVHD)

Donor T-cells react with recipient cells and cause a full body reaction. (reverse of direct/indirect)

Trophoblast

Produce TGFB and IL-4 to stimulate moms T-cells to become T-regs or TH2 to not react to the child. Develops into placenta

Fetal Immune development Organs

-Yolk sac stores macrophages and mast cells

-liver develops and hosts stem cells

-Bone marrow develops and becomes major immune site

Placenta

Separates mom and baby immune systems so you don’t react to each other. Allows for oxygen exchange without contact.

Acquired Tolerance in pregnancy

Consumption or exposure to fathers sperm teaches mothers body it’s not harmful so when you’re pregnant and exposed to baby MHCs you’re less likely to react and miscarry