Immuno midterm

what are Hematopoietic stem cells become

many types of blood cells

how does the INNATE immune system recognize pathogens

use PRRs to recognize PAMPs/DAMPs

Humoral type of PRR

compliment system, antibodies, antimicrobial molecules

cellular type of PRR

neutrophils, macrophages, mast cells, lymphoid, basophils, eosinophils

what is Primary Ciliary Dyskinesia (PCD)

the cilia in the nasal cavity, respiratory track, and inner ear are malformed. This causes recurring bacterial infections due to the impaired mucosal function. Autosomal recessive. Mostly sheep dogs, springer spaniel, newf

what are sentinel cells

macrophages, dendritic cells, mast cells

they recognize and respond to invading microbes. Have PRRs

How do neutrophils kill pathogen after phagocytosis

2 ways-

respiratory burst

Neutrophil granules

what is respiratory burst (neutrophils)

neutrophil releases hydrogen peroxide and bleach

what are the neutrophil granules used for killing a pathogen

if neutrophil cannot phagocyte a pathogen, it uses NETS to capture and kill the pathogen

liver macrophage

kupffer cell

lung macrophage

alveolar OR intravascular macrophage

what do M1 macrophages do

phagocyte pathogens, are cytotoxic. Activated in 2 stages

2 stages needed for M1 macrophage activation

1- priming. IFN-γ binds to the macrophage to activate it

2- Activation. PAMPs bind to “activated” macrophage, fully activating it

types of cytokines produced by macrophages

IL-1, IL-6, IL-12, IL-18, IL-23 (1,6,12,18, 23)

TNF-alpha

how do macrophages kill pathogens

use Reactive Nitrogen Species (RNS) instead of oxygen based chemicals (like neutrophils) for killing

predominant macrophage in humans, mice and dogs

liver macrophages- kupffer cells

predominant macrophage in horses, pigs and cats

lung macrophage- intravascular/alveolar cells

what is Chediak-Higashi syndrome

neutrophils are unable to ingest and kill pathogens

autosomal recessive gene mutation on the LYST gene

clinical signs of Chediak-Higashi syndrome

recurring bacterial infections, coat color dilution, changes in eye color, cataract at early ages, prolonged bleeding time due to low platelets

mostly persian cats

which protein in the compliment system is important

C3

what triggers the classical pathway

ab binding to ag

(adaptive immunity)

what triggers the alternate pathway

compliment protein coming into contact with a pathogen directly

(innate immunity)wh

what does C3b do

opsonization

what does C3b/C5 complex do

MAC attack, terminal pathway

what does C3a do

inflammation

what is opsinization

when a pathogen is covered by complment proteins and/or antibodies

what are CAMs

cell adhesion molecules

stick neutrophils to blood vessel walls to recruit out of blood and into tissue

features of acute inflammation

changes in blood flow, neutrophils recruited, phagocytosis

how do neutrophils get out of blood and into tissue

rolling→ adherence → emigration → chemotaxis

how is neutrophil emigratoin mediated

via integrins and selectins

how is acute imflammation terminated

anti-inflammatory cytokines (IL-10, TGF-beta)

apoptosis of inflammatory cells

short life span inflammatory cells (C3a) die off

chronic v acute inflammation

outcome of chronic inflammation

tissue destruction, fibrosis, granuloma formation, necrosis

lasts months-years

outcome of acute inflammation

resolution, abscess formation

lasts a few days

what causes chronic inflammation

persistent acute inflammation due to un-degradeable pathogens

what is adaptive immunity

specific to antigen, has memory, development takes time

primary v secondary exposure

IgM primary

IgG secondary- shorter lag

rejection of a foreign organ graft is an example of

cell-mediated adaptive immune response

the body rejects the graft bc it senses the cells are difference from itself

what are cytokines

proteins secreted by immune system cells to send signals

what is pleiotropy

cytokines that act on different cell types and produce different response

what is redundancy

lots of cytokines that act on the same cell type to produce one response

hormone v cytokine

hormones signal via endocrine signaling to specific endocrine cells

cytokines signal via all cell signaling types to many types of cells

what is an interleukin

IL

regulate interaction between lymphocyte and leukocyte

what is interfereon

INF

anti-viral function

what is tumor necrosis factor

TNF

anti-tumor cytokine

what is growth factors

regulate hematapoiesus

what are chemokines

recruit immune cells to infection site

primary lymphoid organ

birds- bursa (BCR), thymus (TCR)

mammals- bone marrow (BCR), thymus (TCR)

ruminants- peyers pathes

secondary lymphoid organ

spleen, lymph nodes, peyers patches, bone marrow

what is Gumboro disease

infection of the bursa by a virus. at a young age, lymphoid depletion and inflammation

APC cells

dendritic cells

macrophages

b cells

what is CD40

required for B cell activation (co-stimulatory molecule)

what makes the best Ag

large size, chemical nature, stability, degradability

what is a linear epitope

not effected by ag processing

recognized by BCR, TCR,

what is conformational epitopes

only recognized by BCR

denatured by ag processing

what is a Haptens

light weight compounds (penicillin) that cannot elicit an immune response bc it is too small. Must be bound to a carrier

5 different isotypes

GAMED

A- mucous membrane

G- adaptive

M- initial

D- developing

E- allergic rxn

ab structure

2 light and 2 heavy chains

immunoglobin vs BCR

membrane bound- BCR

secreted- Ig_

immunoglobulin domain

structural building block of the ab

what makes up the light chain

made LAST

made up of a variable and constant region

what makes up the heavy chain

Made FIRST

made up of variable and constant regions

isotype

differences between ab classes

allotype

differences between Ab within the same class (IgA1 vs IgA2)

idiotype

difference in variable region

ID

MHC class 1 structure

made up of

alpha 1 and 2 that form the binding region

beta-2-microglobin that forms one chain

alpha 3 forms the other chain

MHC 2 structure

alpha 1 and beta 1 form the ag binding groove

alpha 2 and beta 2 form the 2 chains

MHC 3

not an ag presenter, codes fora variety of immune proteins

what is polymorphism in terms of MHC diversity

many different versions (alleles) of each MHC gene in the population.

what is polygeny in terms of MHC diversity

multiple different MHC genes, and each gene encodes a different MHC molecule.

what is codominance in terms of MHC diversity

both alleles of a gene are expressed at the same time (advantage)

ENDOGENOUS MHC

all nucleated cells, presents ag from the inside of cell

shows internal signals/status of cell

in the rER

EXOGENOUS MHC

only on APC cells

shows ag from outside after cell has processed it

in the rER

ENDOGENOUS example

virus, proteasome

EXOGENOUS example

bacteria, fungus

what is important about CD79

used by BCR, spans the membrane to send signal to nucleus

2 ways B cells can be activated

t cell independent activation- ag binds to BCR, makes plasma cells and antibodies (no memory)- makes IgM

t cell dependent activation- Th2 cells activate B cells (memory)- makes IgG

t cell dependent activation explained

ag bound to TCR is processed and activates the TCR. Then the TCR expressed CD 154 which binds to th e Bcell. This causes the Bcell to release CD86 which triggers B cell growth and differentiation

what is somatic hypermutation

happens in the dark zone of secondary lymphoid organ

rapid BCR mutation

what is affinity maturation

happens in the light zone of secondary lymphoid organ

selection for BCR that binds most strongly to the ag

what is a myeloma

a cancerous plasma cells

that causes heart failure, bleeding disorders, etc

2 types of t cells and what they produce

αβ TCR- need ag presented on MHC, make CD4 (Th 1, Th2, Th 17, Treg)/CD8 cells

γδ TCR- do not need ag presented on MHC, make IFN-γ to kill cells via perforins/granzymes (like CD8 cells)

helper T cell populations

Th1, Th2, Th17, Treg

Th 1 cell effector cytokines

INF- γ

TNF- alpha

IL-2

Th2 effector cytokines

IL-4

IL-5

Th17 effector cytokines

IL-17

Treg effector cytokine

IL-10

IL-35

TGF-beta

TCR structure

have one chain and use CD3 to signal to the nucleus

signal 1 & 2 for TCR

when the TCR binds to an ag and begins to turn on (signal 1)

checks to see if TCR is actually bound to ag vis costimulation (signal 2)

signal 1 only= anergy, turned off

signal 2 only= nothing

what is CTLA 4 and why is it important

Cytotoxic t lymphocyte antigen 4

an inhibitory receptor on T cells that helps turn down T-cell activation

after signal 1 and 2 T cell activation, CTLA4 is made to turn off actuavtion

what is a superantigen

ag crosslinks to a nonspecific TCR MHC

causes toxic shock

2 ways CD8 cells kill

intrinsic pathway

extrinsic pathway

intrinsic CD 8 pathway

uses perforins and granzymes/serine proteases

some also use TNF-beta

extrinsic CD 8 pathway

CD95 L is expressed on activated T cells and NK cells, caspases cause the target cell to undergoes apoptosis

how do NK cells work

recognize absense of MHC 1 and stimulate the cell to undergo apoptosis

2 types of NK receptors

inhibitory signal binds to normal MHC 1 and inhibits apoptosis

activation signal has no binding to MHC 1 and activated apoptosis

horses and mice dont have Nk cells and instead have

Ly49

what is ADCC

antibody dependent cell-mediated cytotoxicity

what makes up humoral adaptive immunity

B cells/antibodies

what makes up cell mediated adaptive immunity

t cells

use phagocytosis, and cytotoxic mechanism