Module 3 Immunology

Father of vaccines

Edward Jenner

What disease was wiped out in the most of the world in only 2 decades?

Polio

Two scientists that discovered that the serum of animals contained antitoxic activity. Year?

Behring and Kitasato. 1890

passive immunity

Short term protection by transferring premade antibodies from another host

What are the two goals of vaccines? [finish]

Keep pathogen from infecting or lower the amount of pathogens that take over and prevent severity

sterilizing immunity

completely trying to prevent infection through neutralizing antibodies

Why can’t T cells block infection?

They need MHCs, which shows that infections has already taken place, they can’t sterilize because they DO NOT directly attack pathogens

What are the 7 vaccine platforms?

1. killed/inactivated

2. attenuated

3. subunit

4. recombinant vector

5. nucleic acid toxoid

6. polysaccharide

kill/inactivated vaccine

killed with chemicals (usually against viruses)

attenuated vaccine

weakened form of pathogen

subunit vaccine

proteins from the pathogen

recombinant vector

use a bacteria or virus to express proteins from another pathogen

nucleic acid vaccine

insertion of mRNA or plasmid DNA

toxoid vaccine

inactivated versions of a toxins (protein)

polysaccharide vaccine

carb subunits and can be linked to a conjugate (protein)

MHCs present which type of molecules? Which do they NOT typically present?

peptides; polysaccharides and lipids

T/F some pathogens can change their surface antigens to evade antibody binding.

True

Experimental autoimmune encephalomyelitis (EAE)

an animal model of multiple sclerosis

If mice are given myelin basic protein without adjuvant, what will happen?

no paralysis because of peripheral tolerance (anergy)

adjuvant

generates signal 2 (co-stimulation) in vaccines to prime B and T cells

What is the median age for cancer diagnoses?

70

Oncogenesis

accumulation of mutations in multiple genes

What is the difference between an oncogene and a tumor suppressor gene?

tumor suppressor gene stops cell cycle which mutates when cancer is formed. Oncogenes promote the cell cycle.

T/F oncogenesis can create novel epitopes.

True

William Coley

discovered that the immune system of an individual can be used to fight cancer.

Immunotherapy

Pioneered by William Coley. Idea that the immune system can fight off its own cancer

tumor specific antigens

antigens of mutant peptides that are found on the tumor only

tumor associated antigens

overexpression of self peptides or reactivation of embryonic genes

neoantigen quantity

How many neoantigens a tumor produces

neoantigen quality

How immunogenic the neoantigens are

T/F long term survivors have a decrease in neo antigen quality

False

5 mechanisms by which tumors avoid immune recognition

• low immunogenicity

• tumor treated as self antigen

• antigenic modulation

• tumor-induced immune suppression

• tumor-induced privileged site

low immunogenicity

No peptide-MHC ligand, no adhesion molecules, no co-stimulatory molecules

Tumor treated as a self-antigen

No co-stimulation, so T cells become tolerant

antigenic modulation

antibody against tumor antigen induces endocytosis of antigen into tumor cell and the antigen is lost

tumor induced immune suppression

Factors like cytokine release prevent T cells from acting on tumor directly

tumor induced privilege site

physical barrier of tumor, like scar tissue

CD20

a receptor found on tumor cells and all B cells, could be used as a treatment but would attack B cells also

immunotoxins

targeted anti-cancer agents that combine an antibody and a toxin

checkpoint therapy

reawaken T cell function (CTLA-4 and PD-1 receptors) that was turned off by inhibitory molecules

T/F an anti-PD1 antibody can be used to increase the abundance of tumor infiltrating lymphocytes

True

What cytokine is typically released when fighting against a helminth worm?

IL-4

What antibody is typically released when fighting against a helminth worm?

IgE

What T cell responds to IL-4?

TH2

• What 4 cytokines do TH2 cells release and what do they do?

• IL-4: promotes class switching to IgE

• IL-5 and IL-9: promote recruitment of eosinophils and mast cells

• IL-13: stimulates mucus hypersecretion and collagen production

4 types of granulocytes

• neutrophils

• eosinophils

• basophils

• mast cells

allergen trap

IgE antibodies bind to multivalent antigen and Fc portion binds to mast cell. Mast cell then releases granules containing histamines and inflammatory mediators.

FcεRI receptor

binds to IgE antibody bound to multivalent antigen

cross-linking

binding to multiple receptors which is critical for mast cell activation

T/F mast cells are specific to 1 type of Ig

False, they can bind to multiple types of Igs for different types of allergens

What happens when mast cells bind to IgE?

mast cells become sensitized and release molecules that can cause excess fluid, mucus production, hard-breathing, coughing, etc. (to expel parasite)

What type of cell attacks parasite larvae that’s coated in IgE?

eosinophils

How does mast cells become activation affect the GI tract?

diarrhea and vomiting

How does mast cells become activation affect the eyes, nasal passage, and airway?

congestion, wheezing, coughing, phlegm

How does mast cells become activation affect the blood vessels?

increase blood flow and permeability leads to anaphylactic shock

T/F eosinohils are kept is high amounts in the tissues for a quicker response to infection

False, they are kept in low numbers because they are extremely toxic to host tissues

T/F eosinophils express FcεRI receptors at rest

False

What role do basophils play in immune responses?

• similar effector functions to mast cells and eosinophils

• may initiate class switching to IgE

sensitization

becoming more responsive to a stimulus after repeated or initial exposure.

What role does TH2 play in sensitization?

APCs in epithelial and mucosal surfaces promote TH2 responses and TH2 cells promote TH2 class switching and IgE production

P-K test

developed to assess reagin activity

Carl Prausnitz

injected serum from someone allergic to fish into his own arm and when he injected fish extract around his body it only reacted where serum was injected

urticaria

hives

Names a few signs of anaphylaxis

• swelling of lips tongue and throat

• low Bp

• hives, itchiness, lightheadedness

• shortness of breath

• pain when swallowing

• vomiting and diarrhea

4 routes of entry of allergen

1. intravenous (high dosage)

2. subcutaneous

3. inhalation

4. ingestion

Intravenous allergen entry leads to…

systemic anaphylactic shock

Subcutaneous allergen entry leads to…

wheal and flare reactions and atopic eczema

inhalation allergen entry leads to…

allergic rhinitis or asthma

ingestion allergen entry leads to…

vomiting, diarrhea, anaphylaxis, etc.

atopy

a predisposition to become IgE-sensitized to environmental allergens

T/F atopic individuals are less likely to develop allergic reactions

False

T/F Eczema is a prolonged allergic reaction of the skin

True

Why is there an immediate and a later response to allergens?

• Early response is local activation of mast cells by allergen cross-linking IgE.

• Delayed response is the production of genes to make effector molecules and recruitment of additional cells

In 1998 _ in 5 children in industrialized countries suffered from allergic diseases such as asthma.

1

hygiene hypothesis

Early-life exposure to microbes helps the immune system develop properly.

Too little exposure (because of modern cleanliness) increases the risk of allergic and autoimmune diseases

4 types of hypersensitivity responses

type 1- allergy and atopy

type 2- antibody mediated

Type 3- immune complex mediated

Type 4- delayed hypersensitivity

Onco means

swelling in Greek

metastatic tumor

spreads to other parts of the body through the bloodstream

CD16

Fc receptor on NK cells that kill tumor cells

Type 1 hypersensitivity

allergy and atopy;

Ag induces cross-linking of IgE bound to mast cells and basophils with release of vasoactive mediators

Type 2 hypersensitivity

antibody mediated;

cell surface antigens mediate cell destruction

What processes cause cell destruction in type 2 hypersensitivity reactions?

1. macrophages recognize Fc receptors

2. activation of complement cascade

3. ADCC by NK cells

Type 3 hypersensitivity

immune complex-mediated hypersensitivity;

large aggregate of antibodies (immune complexes) recognize soluble antigen in the blood

What cell is a major player in type 3 hypersensitivity, explain the process.

neutrophils;

1. immune complexes get deposited in the wall of blood vessel

2. complement gets activated

3. neutrophils get recruited

4. vessel endothelium gets damaged and blood leaks out into dermis

Type 4 hypersensitivity

Delayed-type hypersensitivity;

sensitized T cells release cytokines that activate macrophage causing direct cellular damage

ADCC

antibody-dependent cell-mediated cytotoxicity

Explain how poison ivy works?

1. urushiol oil from plant cross plasma membrane

2. oil attaches to host proteins

3. peptide from proteins get loaded onto MHC class 1

4. CD8 T cells recognize peptides as foreign

5. CD8 T cells cause cell death and chemokine production

What type of hypersensitivity is poison ivy reaction?

Type 4 hypersensitivity

Celiacs disease

damage to small intestine caused by gluten