Exam 2 Flashcards by Alyssa Becker

Serum dilutions used to measure the amount of titer of Ab in serum

Titration

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Measurement of the level of Abs in serum by testing dilutions of the serum for Ab reactivity

Titration

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Inverse of the highest dilution of serum that gives a reaction in an immunological test

Titer

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Lowest dilution which we still have a response

Titration

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More diluted sample = more antibodies in serum initially

Titer

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Amount of serum compared to total volume of dilution

Titration

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1 ml of serum + 7 ml of diluent =

1:8 dilution

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Common starting points for serial dilutions

1:2 and 1:10

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Inverse of the highest dilution of serum giving a positive test result

Endpoint titer

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____ = concentration of antibody

Titer

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Which cat has the highest antibody concentration
Cat A 1:4 titer
Cat B 1:256 titer

Cat B 1: 256 Titer

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Four fold rise or 2 serial dilutions in titer (or greater) from acute to convalescent serum indicates

active infection

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Serum collected early after onset of illness

Acute serum

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Serum collected 14-21 days later

Covalescent serum

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T/F Acute and Covalescent samples must be tested in parallel

True

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T/F Samples must be test by the same laboratory

True

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Acute tier 1:8
Convalescent tier 1:32
Does this indicate active infection?

Yes

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Measurement of single cells in a fluid stream

Flow Cytometry

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3 important parts of Flow Cytometry

Size
Complexity
Fluorescence intensity

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T/F Flow cytometry can be used on multiple sample types

True

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Multiple sample types used in Flow Cytometry:

Bacteria or microorganisms
Latex beads or nanoparticles
Cells from peripheral blood, tissues, cerebrospinal fluid

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Cluster of Differentiation (CD) molecules define

cell function/subtype

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Monoclonal antibodies are available to what common CD molecules

Canine CD4

Bovine CD11c

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T/F Flow cytometry can be used to determine the frequency of labeled populations

True

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Antibodies can be conjugated to different ___

fluorescent markers

FSC=

cell size

SSC=

complexity

Green fluorescence is seen with what type of T cells

CD8+ cells

Orange fluorescence is seen with what type of T cells

CD4+ cells

Anti-CD8 linked to

fluorescein

Anti-CD4 linked to

phycoerythrin

B cell lymphomas with (high/low) MHC II co-expression have a better prognosis

High

Immunophenotyping (IP) identifies

leukocyte subsets

Red blood cell surface immunoglobulin for dog with IMHA

Anti-IgM (21%) | Anti-C3 (18%)

Anti-CD4 APC Anti-IFN y FITC What T cell subset

Th1 cell

Anti-CD4 APC Anti-IL-4 Pacific Blue What T cell subset

Th2 cell

Define T helper lymphocytes by cytokine expression profiles

Intracellular Cytokine Staining (ICS)

T helper cells by cytokine expression does 2 things:

1. Identify T cell subsets by fluorescent antibodies to surface CD molecules 2. Permeabilize cells and add fluorescent antibodies to cytokines

Cytokine expression by memory lymphocytes to WNV vaccine antigens

Cytokine expressed by antigen stimulated CD4+ T cells

Phytohemagglutinin plays what role in testing WNV vaccine antigens

Positive control

Does the negative control for WNV vaccine antigen contain CD4+

What does the negative control contain

IFN-y

Heterogenous population is what type of lymphocytosis

reactive

Normal lymphocyte distribution is ____ T cells and ___ B cells

2/3 | 1/3

Antigen receptor (BCR/TCR) in reactive lymphocytosis is (clonal or polyclonal)

polyclonal

Many clones responding to an immunogenic stimulus

polyclonal

Homogenous population is what type of lymphocytosis

Neoplastic

Neoplastic transformation and proliferation of how many clones

Single

Antigen receptor (BCR/TCR) for neoplastic lymphocytosis is (polyclonal/clonal)

clonal

In health CD8 T cells should only account for approximately ___ % of T cells

20%

93% CD8 T cells would indicate

chronic lymphocytic leukemia

RID=

Radial Immunodiffusion

What is an acquired immunodeficiency with adult onset in a horse

CVID | Common Variable Immunodeficiency

CVID has what effects

B cell lymphopenia | hypogammaglobulinemia

Site of T and B lymphocyte development and education

primary lymphoid tissues

Primary lymphoid tissues provide _____ with receptors specific for diverse antigens for secondary lymphoid tissues

T and B lymphocytes

Render T and B cells tolerant to self antigens

Central tolerance

Central tolerance occurs in what tissues

Primary

Thymus

Primary

Bone Marrow

Primary and Secondary

Intestine

Primary in ruminants and horses | can be secondary

Spleen

Secondary

Lymph nodes

Secondary

Urogenital system

Secondary

Mammary glands

Secondary

Respiratory tract

Secondary

Salivary glands

Secondary

Source of stem cells

Fetal Yolk Sac Fetal Liver Bone Marrow

Sites of lymphocyte development and education

Thymus Ileal Peyer's Patches Bursa Bone Marrow

Primary or Secondary and B or T cells: | Thymus

Primary | T cells

Primary or Secondary and B or T cells: | Ileal Peyer's Patches

Primary (ruminants and horses) | B cells

Primary or Secondary and B or T cells: | Bursa

Primary (birds) | B cells

Primary or Secondary and B or T cells: | Bone Marrow

Primary | B cells

Sites of foreign antigen interaction and proliferation

``` Tonsils Spleen Lymph nodes Jejunal Peyer's Patches (GALT) Mucosa-associated lymphoid tissue (MALT) Bone Marrow ```

Primary lymphoid organs: B cell development

Bone Marrow Ileal Peyer's Patches Bursa

B cell development of Bone Marrow occurs in

Primates and rodents

B cell development of Ileal Peyer's Patches occurs in

Ruminants and horses

B cell development of Bursa occurs in

Birds

The most important event in the development of a lymphocyte is

Generation of the antigen receptor

Membrane bound immunoglobulin (Ig)

BCR

Immunoglobulin structure of BCR includes

2 heavy chains (H) 2 light chains (L) Linked by disulfide bonds

BCR has a signal transducing component consisting of

CD79 a and B chains Within the cell membrane

Hallmark of humoral immunity is

specificity of the immune response due to gene rearrangment and somatic hypermutation

Random selection of gene segments resulting in genetic diversity of BCR (and TCR) occurs during

Lymphocyte development

Gene rearrangment occurs in (primary or secondary) lymphoid organs

primary

Random selection of gene segments resulting in genetic diversity of BCR and TCR occurs during lymphocyte development and is known as

Gene rearrangment

High frequency mutations in ___ region of Ig genes = Somatic Hypermutation

variable region

High frequency mutations in variable region of Ig genes occurs after what

B cell activation

High frequency mutations in variable region of Ig genes after B cell activation results in

increased affinity for antigen

Somatic hypermutation occurs in

mature lymphocytes in the germinal center of the lymph node

Somatic hypermutation occurs in (primary or secondary) lymphoid organs

Secondary

High frequency mutations in variable region of Ig genes after B cell activation resulting in increased affinity for antigen is known as

Somatic Hypermutation

Fc region includes

2 Constant Heavy regions

Fab region includes

``` 1 Constant Heavy 1 Constant Light 1 Variable Heavy 1 Variable Light Antigen binding site ```

Biological activity occurs in which regions

Constant regions

2 types of Peyer's Patches

Continuous | Discontinuous

Continuous Peyer's Patches are in

The ileum

Continuous Peyer's Patches involute by

15 months

Continuous Peyer's Patches include B or T cells

B cells

Discontinuous Peyer's Patches are in

Jejunum

Discontinuous Peyer's Patches involute by

They don't! They are life long

Discontinuous Peyer's Patches have B or T cells

30% T cells

Continuous Peyer's Patches are (primary or secondary) lymphoid organs

Primary

Continuous Peyer's Patches are found in

Ruminants and horses

Discontinuous Peyer's Patches are (primary or secondary) lymphoid organs

Secondary

Sites of rapid B cell proliferation

Continuous Peyer's Patches

Continuous Peyer's Patches reach maximal size and maturity when

Before birth

At the site of rapid B cell proliferation 2 things happen

1. Most cells undergo apoptosis | 2. Survivors released into circulation

T/F Bursa of Fabricius is only found in birds

True

What is the round sac located just above the cloaca

Bursa

What is the hollow sac with folds of epithelium containing lymphoid follicles

Bursa

When is the Bursa at its greatest size

1-2 weeks after hatching THEN IT SHRINKS

Function of the Bursa

Generate BCR diversity

Structure of the Bursa

Follicular epithelium

Lymphoid follicles contain 2 parts

Cortex and Medulla

What happens in the cortex

B cells proliferate

Rearrangement of genes occur in which part of lymphoid follicles

Cortex

What part of the follicle is the pale center

Medulla

Negative selection of self reactive B cells (central tolerance) occurs in which lymphoid follciles

Medulla

What happens in the medulla

stromal cells present self antigens to B cells

If there is NO MHC expression there is no

Positive selection

Average percentages of B lymphocytes in blood

20%

Can breed differences account for inter-species variability in B cell percentages

Yes

B lymphocytes 7-30%

Dog

B lymphocytes 6-50%

Cat

B lymphocytes 17-38%

Horse

B lymphocytes 13-38%

Pig

B lymphocytes 11-50%

Sheep

B lymphocytes 16-21%

Cow

Bursectomy is the removal of

Ileal Peyer's Patches

B cells constitute approximately what percentage of the circulating pool of lymphocytes

20%

During a Bursectomy the total circulating lymphocyte (t and B cells) pool slightly (increases or decreases)

decreases

During Bursectomy humoral immunity (antibody concentration) markedly (increases or decreases)

decreases

During Bursectomy which component markedly decreases

Antibody concentration

During Bursectomy which component slightly decreases

Total lymphocyte count

What is a lymphoepithelial organ

Thymus

What organ is located in anterior mediastinum over the heart

Thymus

The cortex is lymphocyte (rich/poor)

Rich

Thymic epithelium is visible in

Medulla

Cortex is (dark/light) area

Dark

Medulla is (dark/light) area

Light

Epithelial outgrowth of third pharyngeal pouch =

Thymic epithelial reticulum

Lymphoid progenitors from bone marrow migrate to thymus and become

Thymocytes

Thymocytes mature to

T lymphocytes

Where do lymphoid progenitors come from

Bone marrow

Lymphoid progenitors migrate to

Thymus

When Thymocytes mature to T lymphocytes what 3 things occur

1. Develop T cell receptor (TCR) 2. Become class restricted 3. Tolerized to self

What is a heterodimer of 2 chains

TCR

which 2 components are prevalent in ruminants

Gamma and delta

which 2 components are most numerous

Alpha and beta

(Few/Many) genes encode for the antigen receptor

Many

Beta and delta chains have which regions

Variable (V) Diversity (D) Junctional (J) Constant (C)

Which components have V, D, J and C regions

Beta and delta

V region

Variable

D region

Diversity

J region

Junctional

C region

Constant

Alpha and Gamma chains have which regions

Variable (V) Junctional (J) Constant (C)

Which components have V, J and C regions

Alpha and gamma

TCR =

antigen recognition

TCR co-receptor required for signal transduction

CD3

T cell development | 1st step

Proliferate and rearrange TCR genes

Do delta,gamma and alpha, beta compete for expression

Yes

If gamma, delta is expressed what happens to the gamma, delta bearing TCR

Leaves the thymus

If alpha, beta is expressed what happens

Surface molecules are expressed on developing thymocytes

CD3

Co-receptor

Double positive

CD4 and CD8

Where are T cells educated

Thymus

Thymocyte proliferation and TCR development occurs in

Cortex

Positive selection =

Class Restriction

Negative selection =

Self-Tolerance

What happens when T cells recognize antigens presented by thymic epithelial cells on MHC class I or class II molecules

Class Restriction

Cells with TCR that can bind MHC plus Ag are (positively or negatively) selected in the thymus

Positively

Positive selection occurs where

Thymus

Cells lacking TCR capable of binding to MHC peptide undergo

apoptosis

Approximately what percentage of T cells die in the thymus

98%

A huge diversity of TCRs are possible, what proportion of these will bind to self-MHC

Small proportion

Receptor binds self peptide: self MHC class I

Matures to CD8+ T cell

Receptor binds self-peptide: self-MHC class II

Matures to CD4+ T cells

Class restriction =

Binding to MHC I or II leads to CD8 or CD4 T cell subset

Double positive thymocytes

self peptide binds to self MHC class

Single positive thymocytes

CD8 or CD4

CD8 cells are

Cytotoxic

CD4 T cells are

Helper cells

What is the exception in CD4+CD8+ in circulation

Pigs possess up to 60%

T cells must not respond to self antigens during (positive or negative) selection

Negative selection

T cells with TCR that can bind self MHC plus self Ag are

Negatively selected

Negative selection occurs where

Thymus

Negative selection is similar to central tolerance in B cells in which way

Deleted by apoptosis

Cells that successfully emerge from the thymus are

self tolerant

Goldilocks principle refers to

T cell selection

Too weak of binding to self peptide

cell dies

Too strong of binding to self peptide

Cell dies

Binding to self peptide presented on MHC molecules must be

Just right

Moderate binding

Cell lives

What gene encodes for self peptides

AIRE

Examples of AIRE gene

Insulin Thyroid hormone Collagen

AIRE stands for

Autoimmune regulator gene

What controls expression of >400 tissue specific proteins

AIRE

AIRE gene is expressed by what cells within MHC molecules

Thymic medullary epithelial cells

AIRE gene is important for developing thymocytes to become

self-tolerant

What happens to individuals that lack AIRE gene

Autoimmune Polyendocrinopathy Polyglandular autoimmune syndrome

Cortical epithelial cell mediates

positive selection

Cortical epithelial cell mediating positive selection =

MHC class restriction

Dendritic cell mediates

Negative selection

Dendritic cell mediating negative selection =

Self tolerance

What happens when TCR genes rearrange

Receptor is expressed

Earliest lymphocyte precursors enter the thymus in the

Medulla

After lymphocyte precursors enter the thymus in the medulla they move toward

Cortex

In the cortex lymphocytes proliferate and mature into

double positive (CD4+ CD8+) thymocytes

When they proliferate and mature into double positive thymocytes they generate a

TCR

Thymocytes are screened by

Positive (class restriction) and negative (self tolerance) selection

Where does thymocyte screening occur

Thymic cortex

Cortico-medullary junction contains mature

single positive (CD4 or CD8) T cells

Single positive T cells leave

Thymus

When T cells leave the Thymus they enter

Blood stream

Average percentages of T cells in blood of adult animals

50-65%

T cells 31-89%

Cat

T cells 46-72%

Dog

T cells 38-66%

Horse

T cells 45-57%

Pig

T cells 56-64%

Sheep

T cells 45-53%

Cow

Do breed differences count for differences in percentages within a species

Yes

Thymus involution occurs when in mice

within 3 weeks

Thymus occurs when for humans

During puberty

what happens when the thymus is involuted

replaced by fat but small amounts of functional lymphoid tissue remain

Mice thymectomized at birth have what 2 things occur

1. Susceptible to infection | 2. Fail to grow

Gene mutations resulting in absent or deteriorated thymis

Nude mice

Nude mice have what 5 issues

1. No T cells in secondary lymphoid tissues 2. No T cells in circulation 3. Defective rejection of graft tissue 4. Defective T cell mediated immunity 5. Antibodies to protein antigens decreased (other antibodies OK)

Develops late in fetal life and persists life-long

Secondary lymphoid tissue

Facilitate antigen trapping

Secondary lymphoid tissue

Collects anitgen presenting cells (dendritic cells) and lymphocytes

Secondary lymphoid tissue

Support clonal expansion of antigen specific T and B lymphocytes (lymphopoiesis)

Secondary lymphoid tissue

In secondary lymphoid tissue antigen specific T and V cell effectors move where

Tissues

Secondary lymphoid tissues retain antigen specific

Memory cells

2 types of secondary lymphoid tissues

Encapsulated | Unencapsulated

Encapsulated secondary lymphoid tissues include

Lymph nodes Spleen Hemolymph nodes/hemal nodes

Unencapsulated secondary lymphoid tissues include

MALT BALT GALT Tonsil

MALT

Mucosal lymphoid tissue

BALT

Bronchial associated lymphoid tissue

GALT

Get associated lymphoid tissue

T cell clonal proliferation occurs in

Paracortex

B cell clonal proliferation occurs in

Germinal Center

Naive cells enter lymph node through

HEV

What flows in lymph

Ag, APC drainage from inflammed tissues

Follicle with germinal center is CD3 positive or negative

Negative

Paracortex (T cells) and Immunohistochemistry with CD3 antibody labels what cells

T cells

Reactive lymph nodes have smaller or larger follicles

Larger

Reactive lymph nodes also show what due to larger follicles

Germinal centers

What are the 2 types of lymph nodes

Quiescent | Reactive

How does antigen get to lymph node to stimulate an immune response

DC take up bacterial antigens in the skin and enter a draining lymphatic vessel

After DC enter draining lymphatic vessels then what

DC bearing antigen settle in T cell areas

Lymph flow and Ag, APC drainage from inflamed tissues enters

Afferent lymphatics

After Naive T and B cells circulating in blood enter the lymph node via HEV they

Seek their antigen in the paracortex

T and B effector cells and antibodies leave via

efferent lymphatics

After effector cells leave efferent lymphatics where do they go

through thoracic duct and into systemic circulation

If native lymphocytes in HEV encounter antigen they are

activated

Once lymphocytes are activated what happens

leave the lymph node

Lymphoctes leave the lymph node as

effector lymphocytes

Effector lymphocytes leave through

thoracic duct

Effector lymphocytes can leave circulation and go to

tissues

Primed lymphocytes to got

Antigen

Naive lymphocytes go to

Arteries

Migration to the lymph node through HEV is regulated by

chemokines and adhesion molecules

Movement of a cell in response to a chemical stimulus

Chemotaxis

Family of cytokines with the ability to induce directed chemotaxis

Chemokine

Chemokines tell cells

where to go

Cytokines tell cells

what to do

Transmembrane cell adhesion proteins and signaling receptors

Integrins

Examples of Integrins

CD11b | CD18

___ are sticky for naive lymphocytes

HEV

HEV allow only _____ into lymph nodes

lymphocytes

L selectin is on

Lymphocyte

CD34 is on the

endothelium

L selectin is what CD molecule

CD62L

L selectin on lymphocytes bind to what

CD34

HEV have what type of endothelium

Cuboidal

Intracellular Adhesion Molecule 1

ICAM1

Leukocyte Functional Antibody 1

LFA1

When CD62L (L selectin) interacts with CD34 or GlyCAM1 on HEV it causes (loose or tight adhesion)

Loose adhesion

LFA1 binds tightly to

ICAM1

When LFA1 binds tightly to ICAM1 it causes

Tight adhesion and diapedesis

CCR7 homes T cell and DC to

CCL19 and CCL21

CCL19 and CCL21 are expressed in the

Paracortex

CXCR4 on DC homes to

CXCL12

CXCL12 is expressed in the

Paracortex

CD62L is on T cell or DC cell

T cell

CXCR4 is on T cell or DC cell

DC cell

CCR7 is on T cell or DC cell

Both

CCR7 corresponds to what CC on Paracortex

CCL19 and CCL21

CXCR4 corresponds to what CX on paracortex

CXCL12

Effector T cells shed

CD62L and CCR7

Why do T cells shed CD62L and CCR7

To get into peripheral tissues where inflammation is

T cells recirculate through blood and peripheral lymphoid tissues every

12-24 hours

T cells enter a lymph node across HEV in the

Cortex

T cells monitor antigen presented by

Macrophages and dendritic cells

T cells that do not encounter specific antigen leave the node via

Efferent lymph

T cells that encounter specific antigen proliferate and differentiate to

effector cells

Naive B cells loop through lymphoid system for up to ___ days

100 days

Naive B cells loop through lymphoid system seeking

antigen

Naive B cells receive ______ on each pass through the lymph node follicle

survival signals

Chemokine CCL21 attracts what cells to HEV

Immature B cells

Chemokines ___ and ___ attract B cells into lymph node

CCL21 and CCL19

Chemokine ___ attracts B cells into the primary follicle

CXCL13

CXCL13 attracts B cells into the

Primary follicle

CCR7 on B cells homes through HEV to ___ and ____ in paracortex

CCL19 and CCL21

CXCR5 on B cells homes to ___ in lymph node follicle

CXCL13

CXCL13 is located where

Lymph node follicle

B cell has CD62L and ___

CXCR5

Lymphocytes migrate to the

Lymph node

Where do naive T cells come from

Thymus

Where do naive B cells come from

Bone marrow Peyer's Patches Bursa-birds

How does DC and ag enter the lymph node

Peripheral tissues | Diapedesis into lymph node and follow chemokine gradient

Naive CD4 T cells are activated by

Antigens

Antigens that activate Naive CD4 T cells are presented by

DC in lymph node

Naive B cells activated by antigen are trapped where

T cell zone of the lymph node

Naive B cells are trapped in what zone of the lymph node

T cell zone

Antigen-activated B cells present antigen to

Helper T cells

When B cells present antigen to helper T cells it forms what

cognate interactions and conjugate pairs

Recirculating naive T cells enter the which part of the lymph node

Paracortex

How do naive T cells enter the lymph node

HEV

T cells that encounter specific antigen on DC proliferate and differentiate to

TH subtype

TH subtype is dependent on

DC secreted cytokines

Circulating naive B cells enter which part of the lymph node

Paracortex

How do naive B cells enter the lymph node

HEV

B cells that encounter their antigen stay where

T cell zone

B cells that encounter their antigen process antigen to present to

T cells

How do B cells present to T cells

Peptide on MHC II

B cell zone is where

Follicle

T cell zone is where

Paracortex

TH cells and B cells specific for antigens on the same pathogen form

Conjugate pairs

B cells and T cells recognizing different epitopes on the same antigen =

cognate interaction

4 steps in the lymph node follicle of a reactive lymph node

1. B cell activation 2. Somatic hypermutation 3. Affinity maturation 4. Isotype (class) switch

Naive B cells are located in what zone

Mantle Zone

Germinal Center B cells undergo proliferation and

Somatic hypermutation

Germinal Center B cells are located in what zone

Dark Zone

Interactions with FDC causes

Affinity maturation

Interactions with FDC are located in what zone

Light Zone

Ig class switching and memory B cell formation are located in what zone

Light Zone

What is needed for class switching

Cytokines

What lymph nodes are inside out

Pig

What 4 other animals have inside out lymph nodes

Elephants Rhinos Hippos Dolphins

Why are pig lymph nodes inside out

They do not have lymphocytes in pig lymph

Pig lymph node steps

Bloodstream HEV Lymph node paracortex Efferent vein

Other mammals

``` Bloodstream HEV Lymph node paracortex Efferent lymphatics Thoracic duct ```

Hemolymph also known as

Hemal node

Hemal nodes are what color

Dark red or brown

What is the most prominent in ruminants and deer

Hemal node

Hemal nodes are scattered among blood vessels and function to do what

Filter blood and substances in circulation

Hemal nodes contain B cells where

Cortex

Hemal nodes contain T cells where

Center

Hemal nodes also have what type of cells

gamma, delta

Spleen contains what 2 pulps

Red | White

Which pulp filters blood rather than lymph

Red pulp

Red pulp removes _______ and immune complex coated cells

Aged blood cells

How does Red pulp remove cells

Macrophages

Where are the macrophages located in the red pulp which remove the cells

Sinus

Red pulp salvages _____ and ____ from red cells

Iron | Bilirubin

What pulp has a marginal zone-macrophages (APC)

White pulp

In white pulp what cells reside in follicles

B lymphocytes

Which pulp contains PALS

White pulp

PALS

Periarteriolar sheath

What cells do PALS contain

T cells

White pulp does not have

HEV

Sinusoidal type of spleen has (abundant or poor) sinuses

Abundant

What type of sinuses do sinusoidal types contain

venous

Which animals store large amounts of blood for quick release

Horse Dog Human

Where do animals store large amounts of blood for quick release

Sinusoidal Type of Spleen

Horses, dogs and humans can do what during exercise

Splenic contraction

What type of spleen has smooth muscle around ellipsoid capillary

Sinusoidal type

Smooth muscle around ellipsoid capillary is most prominent in

Horses

Nonsinusoidal type spleen have (abundant or poor) sinuses

Poorly developed

Nosinusoidal type are most common in

Cats | Ruminants

Urogenital is (primary or secondary) lymphoid tissue

Secondary

Where do memory cells and plasma cells colonize

Bone Marrow

Can Bone Marrow act as a secondary lymphoid tissue

Yes

Second dose of antigen causes bone marrow to release large quantities of

Antibodies

Second dose of antigen causes bone marrow to release large quantities of antibodies in which animals

Rodents

Second dose of antigen causes what to release antibodies

Bone Marrow

``` Thymus : Classification Source of Immune Cells Interact with Foreign antigen Interact with Self antigen Positive or negative selection ```

``` Primary T cells N Y Positive and Negative ```

``` Bursa: Classification Source of Immune Cells Interact with Foreign antigen Interact with Self antigen Positive or negative selection ```

``` Primary (Birds) B cells N Y Negative only ```

``` Ileal Peyer's Patches: Classification Source of Immune Cells Interact with Foreign antigen Interact with Self antigen Positive or negative selection ```

``` Primary (Ruminants, Horses) B cells N Y Negative only ```

``` Bone Marrow: Classification Source of Immune Cells Interact with Foreign antigen Interact with Self antigen Positive or negative selection ```

``` Primary and Secondary Lymphoid progenitor B cells Y Y Negative only ```

``` Jejunal Peyer's Patches: Classification Source of Immune Cells Interact with Foreign antigen Interact with Self antigen Positive or negative selection ```

``` Secondary Neither Y N N ```

``` Lymph Nodes: Classification Source of Immune Cells Interact with Foreign antigen Interact with Self antigen Positive or negative selection ```

``` Secondary Neither Y N N ```

``` Spleen: Classification Source of Immune Cells Interact with Foreign antigen Interact with Self antigen Positive or negative selection ```

``` Secondary Neither Y N N ```

Intracellular protozoan parasite

Leishmania sp.

Leishmania parasite is taken up by

Macrophages

Leishmania is transmitted by

Sand flies

Is Leishmania endemic in many countries?

Yes

Where is it comon

South/central America Africa Asia Southern Europe

What causes a disseminated infection in dogs and humans

Visceral Leishmaniasis

What causes the dog not to mount good cell mediated immunity

Visceral Leishmaniasis

Leishmania has a high incidence in what breeds

Foxhounds | Breeds in Spain and France

Leishmania has clinical signs of

Enlarged lymph nodes Hepatomegaly Splenomegaly

Resistant individuals develop ___ which resolves

Cutaneous form

What step of the Leishmania life cycle is this: Promastigote stage in Sandfly gut migrates to proboscis and is injected into skin during blood meal

What step of the Leishmania life cycle is this: Promastigotes taken up by Macrophages and transforms into Amastigote stage

What step of the Leishmania life cycle is this: Sandfly takes blood meal and ingests infected macrophages

what step of the Leishmania life cycle is this: Amastigotes transform into Promastigotes

Leishmania life cycle basic points:

1. Promastigote injected into skin 2. Promastigotes taken up b macrophages Transforms into Amastigote stage 3. Sandfly ingests infected macrophages 4. Amastigotes transform to Promastigotes

Susceptible dogs have 3 major changes

1. Defect in the NRAMP gene 2. Helper cells do not produce IFN y 3. High concentration of antibody

NRAMP

Natural Resistance Associated Macrophage Protein

Defect in NRAMP was reported in dogs from where

Spain and France

Helper cells do not produce IFN y following what

Stimulation by Leishmania antigen

High concentration of antibody against Leishmania is present where

In the blood

What does NRAMP do

Transports divalent ions

Transports divalent ions Fe2 out of the phagosome

NRAMP

Fe out of the phagosome competes with

Bacteria's siderophore pump

NRAMP transports divalent ions out of where

Phagosome

Important parts of Leishmania infection to consider

- Macrophages - Antigen/antibodies - Complement system - Serolgy: Application of antigens and antibodies

What immune mechanism plays a protective role against Leishmania

Macrophages and NRAMP | INF y brings in M1 activating macrophages

Why are liver, spleen and lymph nodes the principle organs enlarged

They are the primary organs of pathogen clearance | Recruit inflammatory molecules

How does a defect in NRAMP decrease the innate immune response to the parasite

Ability of the macrophages to fight phagocytosed microbes is reduced

Which stage of Leishmania (Promastigote or Amastigote) would be most susceptible to antibody and/or complement activation

Promastigote | Extracellular stage

What role does IFN y play in macrophage defenses against the intracelluar stage of the parasite

Critically needed to activate macrophages to differentiate into - M1 Macrophages: NO production/ROS/Lysozyme/Elastase - Lack of IFN y -Inefficient/Ineffective Macrophage actiation

2 tests that can be used to confirm Leishmania infection

PCR: Parasite SNA IFA/Flow Cytometry: Presence of parasite ELISA/Agglutination test/Western Blot-Anti-promastigote antibodies

Major Histocompatibility Conplex was discovered based on

Graft Acceptance or Rejection

Graft acceptance or rejection represents

self recognition

Cluster of closely linked genes

Locus

Locus of genes control presentation of ___ in APCs

Protein Antigens

what controls presentation of protein antigens in APCs

Locus

What is the requirement for peptide to be bound in an MHC molecule to elicit an immune response

MHC restriction

MHC restriction requires peptide to be bound to

MHC molecules

Peptide bond to MHC molecule elicits what

An immune response

Antigen Presenting Cells use ____ to bind and present antigens

Receptors called MHC molecules

APCs do what

bind and present antigens

what receptors do APCs use

MHC molecules

MHC molecules are encoded by genes located within the

Major Histocompatibility Complex

Classical MHC molecules are (highly or very little) polymorphic

Highly

Enormous variety of inherited structural variations that permit each individual animal to respond to different antigens

Polymorphic

Inherited structural variations

Classical MHC molecules

what permit each individual animal to respond to different antigens

Classical MHC molecules

Class I MHC molecules are found on

all nucleated cells

Function of Class I MHC molecules

present endogenous antigens to CD8+ T cells

what class of MHC molecules present endogenous antigens to CD8+ T cells

Class I

Class II MHC molecules are largely restricted to

professional APCs (Dendritic cells) (Macrophages) (B cells)

Function of Class II MHC molecules

Present exogenous antigens to CD4+ T cells

What class of MHC molecules present exogenous antigens to CD4+ T cells

Class II

Class III MHC are (classical or non-classical)

Non-classical

Which class of MHC contains a mixture of genes, some of which encode complement components

MHC III

Function of Class III MHC

Encode complement components

3 major classes of genes located within the MHC grouped in regions

Class I Class II Class III

MHC molecules are grouped together by

regions

What class has receptors for endogenous antigen found on most nucleated cells

Class I

What class has a mixed group of proteins including some complement components

Class III

What class has receptors for exogenous antigen predominantly found on antigen presenting cells

Class II

T/F Arrangment of gene regions within MHC is different for different species

True

ELA

Horse

BoLA

Bovine

SLA

Pig

CLA

Dog

FeLA

Cat

H2 in mice

Rodent

HLA

Primate

II, III, I -centromere

Horse | ELA

centromere-IIb, IIa, III, I

Bovine | BoLA

II, centromere- III, I

Pig | SLA

Centromere-II, III, I

Dog | CLA

II, III, I centromere- I

Cat | FeLA

Centromere-I, II, III, I

Rodent | H-2 in mice

Centromere- II, III, I

Primate | HLA

Function of MHC Molecules

Display cell-associated linear peptides for recognition by T cells

Both self peptides and foreign peptides regulate

Immune responses

Will foreign antigen that cannot bind MHC trigger adaptive immunity

CD4+ T cell + Antigen = | T cell response or not

No response

CD4+ T cell + Antigen + APC= | T cell response or not

Yes

In order for T cells to have a response they need

APC

T cells recognize _____ presented in the context of self MHC

Epitope

MHC has what 2 important features for binding with T cell receptor

Anchor residue of peptide | Pocket of MHC

____ molecules are membrane bond

MHC

Recognition by T cells requires _____ and ____

Cell-cell contact | Peptide

MHC class I present _____ to CD8+ T cells

cytosolic peptides

What MHC class can bind peptides 8-11 amino acids long

Class I

MHC class II present peptides generated from extracellular antigens to ___ cells

CD4+ T cells

MHC class II present peptides generated from _____ antigens to CD4+ T cells

Extracellular antigens

What MHC class binds peptides 10-30 amino acids long

Class II

What 2 things are required for Class MHC and CD T cells to bind

CD3 | TCR

Which MHC class are the ends of the peptide in extended conformation and trimmed

Class II

MHC II binding pockets are (more/less) permissive

MHC molecule can present how many peptides at a time

One

Do MHC molecules have broad specificity

Yes

MHC molecules is capable of presening (different/same) peptides at (different/same) time

Different | Different

______ are critical amino acids which must fit into the binding pocket

Anchor residues

____ sequence between anchors can vary

Peptide

T/F number of amino acids between anchors can vary

True

MHC Polymorphism affects ______

Peptide binding

Changes in the pockets, walls and floor of the peptide binding cleft alter____

peptide MHC interactions

Change in pockets, walls and floor of the peptide binding cleft alter peptide MHC interactions and determine ____

which peptides bind

Products of different MHC alleles bind (different/same) repertoire of peptides

Different

Which MHC class has 3 alpha segments and B2 microglobulin

Class I

Peptide binding cleft in MHC Class I is between what segments

Alpha 1 and Alpha 2

What MHC class has 2 alpha segments and 2 B segments

MHC class II

Peptide binding cleft in MHC Class II is between what segments

Alpha 1 and Beta 1

Transmembrane region has N or C terminus

Which MHC Class has loci A, B and C

Class I

Which MHC Class has loci DP, DQ, DR

Class II

Class I is distributed to what kind of cells

Most nucleated cells

Class II is distributed to what kind of cells

B cells Macrophages Dendritic cells

Function of Class I molecules

Present antigen to CTLs

Function of Class II molecules

Present antigen to T helper cells

What class has the result of T cell mediated toxicity

Class I

What class has the result of T cell mediated help

Class II

What is the different versions of each gene among individuals called

Allele

Group of genes inherited as a set is known as

Haplotype

(Heterozygous/ Homozygous) has 6 molecules on the surface

Heterozygous

(Heterozygous/Homozygous) has 3 molecules on the surface

Homozygous

Heterozygous animals with 2 MHC alleles coded for at each locus express ____ different antigen presenting molecules on the cell surface

Heterozygous or Homozygous generate a more diverse and effective immune response

Heterozygous

Homozygous animals have only 1 MHC a ____ allele coded for at each locus

single

Stable MHC I expression on the cell surface requires

a chain B2 microglobulin bound antigenic peptide

Most individuals are (heterozygous/homozygous) for MHC genes

Heterozygous

MHC Class I express ___ different class I molecules on every cell containing alpha chains encoded by the 2 inhereted alleles

MHC class I contains alpha chains encoded by the 2 inherted alleles of

HLA-A HLA-B HLA-C

Antigen binding site of Class I is formed by the folding of

Alpha 1 and Alpha 2 domains

B2 microglobulin parallels which alpha chain

Alpha 3

Stable MHC II expression on cell surface requires

a and B chains | Bound antigenic peptide

Most individuals express ____ different class II molecules on every cell containing a and B chains

6/8

What are the allels of Class II molecules

1 set of DP 1 set of DQ 1 or 2 of DR

Antigen binding site is formed by the ____ domain from both peptide chains in Class II

variable domains

What cells are required for an effective adaptive immune response

T cells

Antigen specific T cells must be activated by ___

peptide-MHC complexes

Strong selective pressure for pathogens to mutate genes encoding antigens so they can

Evade formation of peptide/MHC complexes

2 ways animals evolved to present pathogen evasion of the MHC

More than 1 type of MHC molecule in each individual Extensive differences [polymorphism] in MHC molecules between individuals

What happens if MHC X was the only type of MHC

Survival of individual threatened | Population threatened with extinction

What if there were only 2 types of MHC molecules Pathogen evades MHC X

Impact on individual varies with genotype XX-die Variant MHC protects population XY YY -survive

What if there were only 2 types of MHC molecules and the pathogen mutates to avoid both MHC Pathogen evades MHC XY

Survival of individual and population is threatened XX XY YY all die

What protects the population

Variant MHC

Total allele combinations possible

1.7 x 10^18

CD1 molecules are non-classical MHC that bind ____ molecules

Lipid

4 types of CD 1 molecules

CD1a CD1b CD1c CD1d

Recognize lipid structures [14 carbons] not sequences

Glycolipids, phosphatides, mycolic acid | Present to T cells or NKT

Promiscuous CD1 bind to more than 1 lipid molecule

CD1a CD1b CD1c to phosphatides

CD1 has the same arrangment of alpha and beta segments as which MHC class (other than it binds lipids instead of peptides)

MHC Class I

What cells do antigen capture, enzymatic breakdown and peptide presentation to T cells

Professional APCs

APCs present peptides to what cells

T cells

T cells only recognize ____peptides bound on MHC molecules

linear

Which 3 cells capture and process foreign antigens for presentation to T cells

DC Macrophages B cells

When DC, Macrophages and B cells capture and process antigens for presentation to T cells it causes what response

Adaptive immune response

Which cells are the most efficient antigen-processing cells

DCs

Only DCs effectively stimulate ____

naive T cells

Immature ___ are found throughout the body [Sentinels]

DCs

DCs are well equipped to do what

capture and process antigens

Once stimulated by ______, DCs mature and become effective in presenting peptides to T cells

Antigens [and PAMPS]

DC cells express high levels of which MHC class on their surface

MHC class II

DCs ingest ___

antigens

DCs break antigens into peptides and present them on their surface MHC molecules where they can be recognized by

T cells

Macrophages also act as

APC

Macrophages are more/less efficient than DCs

Less

Why are macrophages less efficient than DCs

Destroy ingested antigens

B cells act as APC and are especially effective during _____

Secondary immune responses

3 major populations of antigen-presenting cells

B cells DC Macrophages

Only DCs can activate

naive T cells

When DCs active naive T cells they trigger

Primary immune response

Macrophage and B cells don't activate naive T cells they go straight to

Sensitized helper T cell

B cell Dendritic cell Macrophage all lead to

Activation and cytokine synthesis

What cells are the most important full time professional antigen processing cells and Sentinel

Dendritic cells

Only cell with capacity to activate naive T cells

DCs

Extensive dendrites have a large surface area for

Antigen capture and T cell interaction

Immature DCs are good at

Capturing antigen Phagocytosis Pinocytosis

Mature DCs are efficient at

processing antigens and presenting peptides

Mature DCs process antigens and present peptides to naive T cells where

in Lymphoid organs

DCs produce different cytokines depending on binding to

PAMP/DAMP and Alarmins

DCs when bound to PAMP/DAMP and Alarmins lead to

activation of T cell subsets

what is the main function of macrophages

trap and destroy pathogens

phagosomes are very (acidic/basic)

Acidic

which cells cannot engage in prolonged interactions with T cells

Macrophages

Macrophages present antigens to effector and memory cells but not

Naive T cells

B cells process and present protein antigens in blood and lymphoid organs to

Helper T cells

B cells process and present protein antigens in blood and lymphoid organs to helper T cells during

Secondary immune responses

What 2 other cells can also express MHC II but lack efficient antigen processing machinery

Basophils | Neutrophils

Basophils and Neutrophils lack

efficient antigen processing machinery

Dendritic cell uses what molecules for antigen presentation

Costimulator B7 CD28 Naive T cell

Response of antigen presentation to DC=

Effector T cells

Function of DC

Naive T cell activation

Naive T cell activation causes

clonal expansion and differentiation into effector T cells

Response of antigen presentation between macrophage and effector T cell

Killed Microbe

Function of Macrophage

Effector T cell activation

Effector T cell activation =

activation of macrophages (cell mediated immunity)

Response of antigen to B cell =

Antibody

Function of B cell

Effector T cell activation

Effector T cell activation of B cell=

B cell activation and antibody production (humoral immunity)

Cell mediatedy immunity is when

macrophages are activated

Humoral immunity is when

B cells are activated=antibody production

Plasmacytoid DCs originate from

lymphoid precursors

Plasmacytoid Dcs originate from lymphoid precursors which give rise to

DC2-type cells

Myeloid precursors give rise to

Myeloid DCs Follicular DCs Langerhans cells

Myeloid DCs Follicular DCs Langerhans cells all constitute ____

DC1 type

Bone marrow stem cell give rise to what 2 cells

Myeloid precursor | Lymphoid precursor

Lymphoid precursor gives rise to what cells

NK cells T cells B cells Plasmacytic cell

Plasmacytic cell gives rise to what cells

Plasmacytoid DC

Plasmacytoid DC is DC(1/2) cell

DC2 cells

Myeloid precursor gives rise to what cell

Monocyte

Monocyte gives rise to what 3 cells

Myeloid DC Follicular DC Langerhans cell

Myeloid DC Follicular DC Langerhans cell are DC(1/2) cells

DC1 cells

What cells are Immature DC in skin

Langerhans cells

What cells are the origin of histiocytoma in dogs

Langerhans cells

What cell of Mature DC interacts with T cells in the lymph node

Interdigitating DCs

What cells In thymus important for presenting self-antigens to thymocytes (developing T cells)

Thymic DCs

What cells are confined to follicles of lymph nodes, present antigens to B cells as immune complexes

Follicular DCs

What cells are not effective at antigen presentation

Plasmacytoid DCs

What cells are professional producers of IFNa and IFNB

Plasmacytoid DCs

As DCs mature what happens to their function

Change in function

Immature DCs are specialized as

antigen trapping cells

Mature DCs are specialized

Antigen-Processing and Presenting cells

Bone marrow gives rise to what cells

Dendritic cell precursor

Immature dendritic cell are found where

Tissues

Immature dendritic cells do what

Antigen uptake/Processing

Which cell has low surface MHC II

Immature dendritic cell

Which cell has High intracellular MHC II

Immature dendritic cell

Which cell has High FcR

Immature dendritic cell

Which cell has Low CD40, 80, 86

Immature dendritic cell

Which cell has Low IL-12

Immature cell

What products come in between transformation of immature dendritic cell to mature dendritic cell

Bacterial products Inflammatory mediators Cytokines DAMPs

Mature Dendritic cells are found where

Lymphoid organs

What is the function of mature dendritic cell

Antigen presentation

Which cell has high surface MHC

Mature dendritic cell

which cell has low FcR

Mature dendritic cell

Which cell has High CD40, 80, 86

Mature dendritic cell

which cell has high IL-12

Mature dendritic cell

Which cell has DC-SIGN

Mature dendritic cell

DCs polarize ______ responses

Helper T cell

DCs subsets appear to favor different helper T cell subpopulations:

Th1 | Th2

Cells which promote cell mediated immunity

Th1

Cells which promote antibody formation

Th2

Helper cell populations employed depends on _____

cytokines produced by the DCs subsets

what is the key cytokine that determines Th1/Th2 polarization

IL-12

IL-12 determines what

Th1/Th2 polarization

Which cells develop when IL-12 is present

Th1

Which cells develop when IL-12 is absent

Th2

IL-12 is produced by

Macrophages DCs B cells Neutrophils

What cells are the targets of IL-12

T cells and NK cells

``` DC1 has (high/low) IL-12 Th1 or Th2 cell ```

High | Th1

``` DC2 has (high/low) IL-12 Th1 or Th2 cell ```

No IL-12 | Th2

What collects antigen from epithelium and connective tissue

Lymph node

Blood borne antigens are captured by antigen presenting cells in what organ

Spleen

Processing of Exogenous Antigen has 3 steps

1. Antigen is fragmented 2. Antigen binds to MHC class II molecules 3. Antigen is presented on the cell surface with MHC class II

Which step of Processing of Exogenous Antigen is this: Antigen is fragmented

Which step of Processing of Exogenous Antigen is this Antigen binds to MHC class II molecules

Which step of processing of exogenous antigen is this Antigen is presented on the cell surface with MHC class II

Ingested antigens are taken into

Phagosomes

Ingested antigens are fragmented by

Proteases

Peptides are then carried to the endosomal compartments where antigenic peptides are placed in the binding grooves of

MHC class II molecules

Antigen MHC complexes are carried to the cell surface and presented to which cells

CD4+ helper T cells

Newly synthesized proteins are ubiquinated then chopped into

peptides

what chops proteins into peptides

proteasome

Peptides attach to which transporter protein

TAP

TAP (transporter protein) is located in the membrane of

Endoplasmic reticulum ER

Peptides are loaded into the ER lumen where they are placed in which antigen binding groove

MHC I

MHC I peptide complexes are carried to the cell surface for recognition by what cells

CD8+ T cells

Which cells do antigen cross presentation

DCs

Antigen capture | Infected cells and viral antigens picked up by

Host APCs

Process by which DCs (or macrophage) ingests particulate antigens, whole organisms, an infected cell and presents peptides to cytotoxic CD8 T cells

Antigen Cross-presentation by DCs

particulate antigens, whole organisms and infected cell presents why type of antigens

exogenous antigens

Which class presents peptides to CD8

MHC I

T cells recognize antigen using

Membrane bound T cell receptor TCR

TCR=

Membrane bound T cell receptor

``` CD35 FcR H3 CD25 CD2 are (Regulatory receptors, antigen-receptor complex or transport receptor) ```

Regulatory receptor

CD4 or CD8 CD3 TCR are (Regulatory receptors, anitgen-receptor complex, transport receptor)

Antigen-receptor complex

CD71 | is (Regulatory receptor, antigen-receptor complex, transport receptor)

Transport receptor

CD4 or CD8 binds what

MHC molecules

TCR binds what

antigen

CD2 binds what

CD58

CD25 binds what

IL-2

H3 binds what

Histamine

FcR binds what

Immunoglobulins

CD35 binds what

Complement

CD71 binds what

Transferrin

T cells express antigen receptors known as

TCR

TCR consist of paired _____

peptide chains

What are the 2 peptide chains

aB or yS

TCR's ligands are peptides linked to _____ on APCs

MHC molecules

Antigen-binding chains of the TCR connect to a complex signal transducing component know was

CD3

Each TCR is associated with____ or ____

CD4 or CD8 co-receptors

CD4 binds which class on what cells

``` MHC class II molecules on professional APCs ```

CD8 binds which class on what cells

``` MHC class I molecules on all nucleated cells ```

To respond to antigens T cells must bind to ______

antigenic peptides linked to MHC molecules

To respond to antigens T cells must bind antigenic peptides and must also receive co-stimulation from _____

cytokines

Multiple signals sent by an APC are communicated to a T cell through

Immunological synapse

3 major subpopulations of helper T cells

Th1 Th2 Th17

Which T cells are stimulated by IL-12 and secrete IFN y in response

Th1 cells

Which cells generally promote cell-mediated responses

Th1

Which T cells secrete IL-4, IL-13, IL-10

Th2 cells

Which cells generally promote antibody responses

Th2

Which cells develoment is stimulated by IL-6, TGF-B, and IL-23

Th17 cells

which cells secrete IL-17 and promote neutrophil mediated inflammation

Th17

TH1 are stimulated by

IL-12 and IFN-y

TH2 secrete

IL-4, IL-13 and IL-10

TH17 are stimulated by

IL-6, TGF-B and IL-23

TH17 secrete

IL-17

Function of Th1

Promote cell mediated responses

Function of Th2

Promote antibody responses

Function of Th17

Neutrophil mediated inflammation

Which cells (a/B or y/S) are predominant T cells in most mammals

a/B

Which cells (a/B or y/S) are mainly confined to the intestinal wall in humans but predominant circulating T cells in young ruminants and pigs

y/S

y/S are the predominant circulating T cells in

young ruminants and pigs

T cells develop within

Thymus

T cells are distributed in

lymph node paracortex | Spleen periarteriolar sheath

T cell antigen receptors are

TCR: protein heterodimer

T cell antigen receptors are associated with

CD3, CD4, or CD8

Important T cell surface antigens are

CD2, CD3, CD4 or CD8

T cell antigens that are recognized

are processed foreign proteins in MHC antigens

T progeny cells are

Effector T cells and Memory T cells

T cell secreted products

Cytokines

What are the key antigen receptors of the immune system

TCR MHC class I MHC class II BCR

Each TCR is constructed using ________ as building blocks

Immunoglobulin domains

Each TCR binds antigen through the use of

Variable domains

All TCR's are members of what superfamily

Immunoglobulin

T cells are divided into subpopulations based on what 3 things:

1. Antigen receptors they empty 2. Accessory molecules that support their activity 3. Their functions

Antigen receptors T cells employ: 2 groups

aB | yS

Accessory molecules that support T cell activity

CD4 | CD8

Functions of CD4

Helper 1 Helper 2 Helper 17 Regulatory Memory

Function of CD8

Cytotoxic Regulatory Memory

Multipotent HSC leads to B,T and NK cells which leads to

Pro-T cell

TCR and ____ are structurally similar

Ig molecules

Unlike Ig molecules TCR chains do not undergo

Isotype switching or affinity maturation during T cell differentiation

Recognition of Diverse Antigens by TCR entails generation of

Diverse TCR repertoire

What are the 2 mechanisms of generating diversity in TCR

Combinatorial and Junctional diversity

Combinatorial and Junctional diversity depends on 2 things

Somatic VDJ Recombination | N and P nucleotide addition

Which chain has a greater number of V gene segments | alpha or Beta

Beta (67 vs 54)

Which chain has a greater number of diversity (D) gene segments (alpha or Beta)

Beta (2 vs 0)

Which chain has a greater number of joining (J) gene segments (alpha or Beta)

Alpha (61 vs 4)

TCR = 3 x 10^ 6 | Is this the number of possible VDJ combinations in combinatorial or junctional diversity

Combinatorial

TCR= 10^16 | Total potential repertoir with combinatorial or junctional diversity

Junctional

RAG =

Recombination Activating Genes [VDJ Recombinase]

What does RAG do

cut dsDNA

What does Artemis do

Cut hairpin loops

During junctional diversity what enzyme does it need at the end

Terminal deoxyribonucleotidyl transferase

Combinatorial diversity: Antigen receptors are encoded by several gene segments that are separate from one another in the germline and recombine during

Lymphocyte maturation

RAG 1 and RAG 2

Recombination Activating Genes 1 and 2

what enzyme is needed in combinatorial diversity

VDJ Recombinase

Combinatorial diversity is limited by the number of available

V, D and J gene segments

Junctional diversity: During an intermediate stage in the process of VDJ recombination, before breaks in the DNA are repaired overhanging DNA sequences may be generated which are filled by

P nucleotides

TdT

Terminal deoxyribonucleotidyl transferase

TdT catalyzes the random addition of nucleotides that are not part of germline genes to sites of VDJ recombination forming what

N regions

T/F Junctional diversity is almost unlimited

True

Stages of T cell Maturation go through what order of tissues

Bone Marrow Thymus Periphery

What stage of maturation has: Anatomic site: Bone Marrow TCR expression: None Surface markers: c-kit+, CD44+, CD25- Response to antigen: None

Stem cell

What stage of maturation has: Anatomic site: Thymus TCR expression: None Surface markers: c-kit+, CD44+, CD25+ Response to antigen

Pro-T

What stage of maturation has: Anatomic site: Thymus TCR expression: Pre-T receptor (B chain/ pre-T a) Surface markers: c-kit+, CD44-, CD25+ Response to antigen: None

Pre-T

What stage of maturation has: ``` Anatomic site: Thymus TCR expression: Membrane aB TCR Surface markers: CD4+ CD8+ TCR/CD3lo Response to antigen: Positive and negative selection ```

Double positive

What stage of maturation has: ``` Anatomic site: Thymus TCR expression: Membrane aB TCR Surface markers: CD4+ CD8- or CD4- CD8+ TCR/CD3hi Response to antigen ```

Single positive immature T cell

What stage of maturation has: ``` Anatomic site: Periphery TCR expression: Membrane aB TCR Surface markers: CD4+ CD8- or CD4- CD8+ TCR/CD3hi Response to antigen: Proliferation and differentiation ```

Naive mature T cell

Stages of T cell Maturation | occurs in what order:

``` Stem cell Pro-T Pre-T Double positive Single positive immature T cell Naive mature T cell ```

Positive selection occurs where

Periphery

During positive selection naive T cells are transported to ______ by blood

secondary lymphoid organs

What cells do priming during positive selection

DCs

Failure of positive selection leads to

Apoptosis

Maturation and Selection of MHC restricted T cells goes from Bone marrow/fetal liver to ______ then ______

Thymus | Periphery

Weak recognition of class II MHC + peptide leads to

Mature CD4+ T cell

Weak recognition of class I MHC + peptide leads to

Mature CD8+ T cell

No recognition of MHC + peptide

Apoptosis

Strong recognition of either class I or class II MHC + peptide

Apoptosis

Mature CD4+ T cell leads to

Positive selection

Mature CD8+ T cell leads to

Positive selection

Apoptosis causes (positive/negative selection)

Negative selection

Maturation and Selection of MHC restricted T cells goes through which order:

``` Stem cell Double negative (CD4-CD8-) pro-T cell Pre-T cell Double positive (CD4+CD8+) immature T cell Thymocyte ```

(Positive/Negative) selection ensures survival and maturation of T cells whose receptors bind with (low/high) avidity to self MHC + self peptide

Positive | Low -weakly

Positive selection provides _______ to T cells that have properly rearranged both aB chains of the TCR

survival signals

Positive selection provides ___________ to ensure CD4+ and CD8+ T cell subsets are properly matched to the appropriate class of MHC molecule the cell recognizes

Lineage commitment signal

Failure of positive selection =

Death [apoptosis] due to neglect

During (positive/negative) selection developing T cells that have (low/high) affinity for self-antigens are eliminated by apoptosis

Negative | High

High affinity for self antigen eliminated by apoptosis is known as

Clonal deletion

Clonal deletion occurs in (positive/negative) selection

Negative

Positive selection deals with avidity or affinity

avidity

Negative selection deals with avidity or affinity

affinity

Where do naive T cells come from

Thymus

Naive T cells circulate through lymph nodes and find _____ on DCs

Epitopes

Activation of naive T cells in lymph node =

development of effector cells

Activation of effector T cells at site of infection =

eradication of microbe

Signal transduction proteins are classified as

CD3

What is the role of CD4 and CD8 molecules

Serve as Co-Receptors

What do co-Receptors do

Link T cells to the APC

When the T cell is linked to APC what 2 things happen

1. Bind the 2 cells together | 2. Ensure that an effective signal is transmitted between them

CD4 binds to

MHC II

CD8 binds to

MHC I

What is signal I

TCR recognition of MHC-peptide plus Co-receptor binding

Antigen presenting cell

MHC class II, CD4

Abnormal cell

MHC class I, CD8

Role of Co-stimulation in T cell activation

B7 is needed to bind to CD28

Activated APCs (increase/decrease) expression of costimulators, secretion of cytokines

Increase

Activation of APCs by microbes = what type of immune response

Innate Immune Response

Costimulator decificent APC = what T cell response

No response or anergy

What step in T cell activation/inactivation is this: Binding of antigen to the TCR causes T cell to express CD40 ligand (CD154)

What step in T cell activation/inactivation is this: CD154 engages CD40 on the APC

What step in T cell activation/inactivation is this: CD28 is expressed on T cell and CD80/86 are expressed on APC =T cell activation

What step in T cell activation/inactivation is this: Activated T cell express CD152 which has higher affinity for CD80/86 =T cell inactivation

Binding of antigen to TCR causes T cell to express

CD40 ligand (CD154)

CD154 engages _____ on APC

CD40

What CD is expressed on the T cell

CD28

What CD is expressed on APC

CD80/86

When CD28 and CD80/86 are expressed what happens

T cell activation

Activated T cells express

CD152

CD152 has (higher/lower) affinity for CD80/86

Higher

Expressing CD152 causes what

T cell inactivation

Successful stimulation of a T cell requires how many signals | single/multiple

Multiple

T/F T cell may be activated by signals from multiple TCRs

True | Strong signal

Can T cells be activated by co-stimulation

Yes | Strong signal

What causes a weak signal for T cell activation

Binding of 1 antigen

What cells play a part in development of TH1 cells

Macrophages NK cells DC Naive T cell

What factors are important in TH1 cell development

IL-12 | IFN-y

Effector functions of TH1 cells

Macrophage activation | Production of some antibody isotpes

Which TH cell has the effector functions of macrophage activation and production of some antibody isotypes

TH1

Which TH cell uses IL-12 and IFN-y

TH1

Which cells play a part in development of TH2 cells

DC Mast cells Eosinophils Naive T cell

What causes development/need for TH2 cells

Helminths

Which factors are important in TH2 cell development

IL-4 IL-5 IL-13

What is the effector function of IL-4

IgE production

What is the effector function of IL-5

Eosinophil activation

What is the effector function of IL-13

Mucosal secretions

What factor causes IgE production

IL-4

What factor causes Eosinophil activation

IL-5

What factor causes Mucosal secretion

IL-13

Which TH cell uses IL-4, IL-5, IL-13 for development

TH2

Which TH cell has these effector functions IgE production Eosinophil activation Mucosal secretion

TH2

Which cells are important in the development of TH17 cells

DC | Naive T cell

What causes need for development of TH17

Bacteria | Fungi

What factors are important for the development of TH17

``` IL-6 IL-1 TGF-B IL-21 IL-22 IL-23 ```

What is the effector function of IL-17

Inflammation

What is the effector function of IL-22

Barrier function

Which factor causes inflammation

IL-17

Which factor causes barrier function

IL-22

What are the effector functions of the development of TH17 cells

Inflammation | Barrier function

Which TH cell uses IL-6, IL-1, TGF-B, IL-21, IL-23, IL-17, IL-22

TH17

Which TH cell has the effector functions of inflammation and barrier function

TH17

T cells exposed to antigen from Toxocara canis roundworm mount a ____response

TH2

When T cells mount a TH2 response they secrete which factors

IL-4 and IL-5

T cells exposed to PPD antigen from M. tuberculosis mount a ______response

TH1

When T cells mount a TH1 response they secrete which factors

IFN-y and IL-2

Do different antigens trigger distinct TH subsets

Yes

TH2 response and secretion of IL-4 and IL-5 is due to T cells exposed to

Toxocara canis roundworm

TH1 response and secretion of IFN-y and IL-2 is due to T cells exposed to

M. tuberculosis

Signature cytokines of Th1 cell

IFNy

IFNy is a signature cytokine of which T cell subset

Th1

Th1 cells cause what immune reactions

Macrophage activation and IgG production

Macrophage activation and IgG production immune reactions are caused by what T cell subset

Th1

What is the host defense for Th1

Intracellular microbes

Intracellular microbes are the host defense for which T cell subset

Th1

Signature cytokines of Th2 are

IL-4, IL-5, IL-13

IL-4, IL-5, IL-13 are signature cytokines of which T cell subset

Th2

Th2 causes what immune reaction

Mast cell and eosinophil activation IgE production Alternative macrophage activation

Which T cell subset has these immune reactions Mast cell and Eosinophil activation IgE production Alternative macrophage activation

Th2

Th2 has what host defense

Helminithic parasites

Which T cell subset has Helminithic parasite host defense

Th2

Th17 has what signature cytokines

IL-17A, IL-17F, IL-22

Which T cell subset has the signature cytokines IL-17A, IL-17F, IL-22

Th17

Th17 causes what immune reactions

Neutrophilic and monocytic inflammation

Which T cell subset has the immune reactions of neutrophilic and monocytic inflammation

Th17

Th17 has what host defense

Extracellular bacteria and fungi

Which T cell subset has extracellular bacteria and fungi host defense

Th17

which T cells produce cytokines that stimulate CTL differentiation

CD4+ helper T cells

APC + costimulator | CD4+ helper T cell + cytokines

Differentiated CTLs

CD4+ helper T cells produce cytokines that stimulate

CTL differentiation

CD4+ helper T cells enhance the ability of APCs to stimulate

CTL differentiation

CD4+ helper T cells (decrease/enhance) the ability of APCs to stimulate CTL differentiation

Enhance

Which T cells enhance the ability of APCs to stimulate CTL differentiation

CD4+ helper T cells

CD40 + CD4+ helper T cell | Costimulator + CD8+ cytokines

Differentiated CTLs

What factor causes expression of IgG subclasses (IgG1, IgG3)

IFN-y

what factor causes expression of IgE

IL-4

what factor causes expression of IgA

Mucosal tissues, cytokines | TGF-B, APRIL, BAFF

IFN-y stimulates what Ig

IgG

IL-4 stimulates what Ig

IgE

Mucosal tissues, cytokines (TGF-B, APRIL, BAFF) stimulate what Ig

IgA

Which factor activates T cells, B cells, NK cells and macrophages

Interleukin 2

Which T cell subset produces Interleukin 2

TH1

What are the functions of Interleukin 2

Activates T, B, NK cells and macrophages

which factor inhibits Th2 cells, stimulates Th1 cells and Activates NK cells

Interferon-y

Which T cell subset produces Interferon-y

Th1

What are the functions of Interferon-y

Inhibits Th2 cells Stimulates Th1 cells Activates NK cells

Enhanced MHC expression is due to

Macrophage activation

Increased iNOS production is due to

Macrophage activation

Increased nRAMP expression is due to

Macrophage activation

Increased IL-12 production is due to

Macrophage activation

Increased chemokine production is due to

Macrophage activation

Increased integrin production is due to

Macrophage activation

Functions of macrophage activation

``` Enhanced MHC expression Increased iNOS production Increased nRAMP expression Increased IL-12 production Increased chemokine production Increased integrin production ```

Macrophage activation (increases/decreases) MHC expression

Enhances

Macrophage activation (increases/decreases) iNOS production

Increase

Macrophage activation (increases/decreases) NRAMP expression

Increase

Macrophage activation (increases/decreases) IL-12 production

Increase

Macrophage activation (increases/decreases) Chemokine production

Increase

Macrophage activation (increases/decreases) Integrin production

Increase

Interleukin 2 | (activates/deactivates) T cells, B cells, NK cells and macrophages

Activates

Interferon-y (increases/decreases) Th2 cells

Inhibits

Interferon-y (activates/deactivates) Th1 cells

Stimulates

Interferon-y (activates/deactivates) NK cells

Activates

Which factor stimulates B cell growth and differentiation | Activates mast cells

Interleukin 4

Which factor stimulates B cell growth | Mobilizes and activates eosinophils

Interleukin 5

Which factor stimulates T cell growth factor

Interleukin 9

Which factor inhibits Th1 cell function | Suppresses macrophage function

Interleukin 10

Which factor stimulates B cell growth | Suppresses macrophage functions

Interleukin 13

Which T cell subset produces Interleukin 4

Th2

Which T cell subset produces Interleukin 5

Th2

Which T cell subset produces Interleukin 9

Th2

Which T cell subset produces Interleukin 10

Th2

Which T cell subset produces Interleukin 13

Th2

Functions of Interleukin 4

Stimulate B cell growth and differentiation | Activates mast cells

Interleukin 4 | (Activates/deactivates) mast cells

Activates

Functions of Interleukin 5

Stimulate B cell growth | Mobilizes and activates eosinophils

Interleukin 5 | (activates/deactivates) eosinophils

Activates

Functions of Interleukin 9

T cell growth factor

Function of Interleukin 10

Inhibits Th1 cell function | Suppresses macrophage funcction

``` Interleukin 10 (increases/decreases) macrophage function ```

Suppresses

Interleukin 10 (stimulates/inhibits) Th1 cell function

Inhibit

Function of Interleukin 13

Stimulates B cell growth | Suppresses macrophage functions

Interleukin 10 and 13 share what function

Suppress macrophage function

CD4 T regulatory cells are called

Tregs

Tregs express which transcription factor

FoxP3

Tregs secrete which factors

IL-10 | TGF-B

Tregs suppress

autoreactive lymphocytes

What cells suppress autoreactive lymphocytes

Tregs

Dampen immune responses to food antigens and allergens is a function of what cell

Tregs

Dampen antigen specific immune responses to pathogens, tumors and parasites is a function of what cell

Tregs

Tregs dampen which 2 responses

1. immune responses to food and allergens | 2. Immune response to pathogens, tumors, parasites

Which cells may act as innate immune cells with an invariant antigen receptor

y/S T cells

Which immune response is found in skin and uterus

Innate

Which immune response has limited TCR diversity recognizing CD1d associated lipids

Innate

Innate immune response produces which factors

IFN-y and IL-17

IFN-y and IL-17 are produced by which immune response

Innate

Antigen presentation to what T cells

a/B

which immune response is found in GI tract and secondary lymphoid organs

Adaptive

Which immune response has polyclonal TCRs recognizing multiple antigens

Adaptive

Adaptive immune response produces which factors

Th1-IFN-y | Th2-IL-4

IFN-y and IL-4 are produced by which immune response

Adaptive

In adaptive response IFN-y is from which T cell subset

Th1

In adaptive response IL-4 is from which T cell subset

Th2

Th1 produces which factor

IFN-y

Th2 produces which factor

IL-4

Which cells are prominent in neonatal animals and decline with age

yS T cell Antigen Receptors

which cells have high levels in ruminants, pigs and birds

yS T cell Antigen Receptors

yS T cell Antigen Receptors have high levels in which animals

Ruminants Pigs Birds

yS T cell Antigen Receptors (increase/decrease) with age

Decrease

What is the bridge between innate and adaptive immunity

yS T cell Antigen Receptors

yS T cell Antigen Receptors function as ____that enhance the 1st line of immune defense

Lymphocytes

(high/low) diversity of yS TCRs in many tissues suggests that ligands for these receptors may be invariant and conserved

Limited

yS T cells may recognize antigens that are frequently encountered where

Epithelial boundaries | -mucosal tissues and skin

Which cells recognize antigens at the epithelial boundaries (mucosal tissues, skin)

yS T cells

Which cells recognize molecules that may be presented by Non-classical class I MHC like molecules (PAMPs, Phospholipids)

yST cells

Non-classical class I MHC molecules include

PAMP | Phospholipids

yS T cells secrete which cytokines

IFN-y IL-4 IL-17

Which cells secrete IFN-y, IL-4, IL-17

yS T cells

Which cells do not express a TCR and are not antigen specific

NK cells

NK cells do not express a _____

TCR

Are NK cells antigen specific

NK cell killing is triggered by

ADCC

Antibody mediated cellular cytotoxicity

Antigen binds antigens on the surface of

Target cells

___ receptors on NK cells recognize bound antibody

Cross-linking of Fc receptors signals the NK cell to _____

kill the target cell

Target cell dies by

apoptosis

NK cells recognize antibodies bound to cellular targets via

CD16 | FcyRIII

NK cells have recognition of cells with altered ____ molecules

MHC-1 surface molecules

Once Nk cell is activated they kill target cells via

Perforin Granzymes (proteases) TNF-a dependent activation of apoptosis

NK cells also produce what inflammatory cytokine

IFN-y

Dominant inhibition on = (lysis or no lysis)

No lysis

Dominant inhibition off =(lysis or no lysis)

Lysis

Tumor cells lack

MHC-I

Virus infected cells (upregulate/downregulate) MHC-I expression

Downregulate

Transplanted cell express allogeneic

MHC-1

Which cells have a TCR with a unique a chain

NK T cells

All NK-T cells recognize lipids bound to class I MHC like molecules called

CD1 molecules

All NK-T cells recognize

lipids

Nk-T cells rapidly produce

cytokines

Which cytokines do NK-T cells rapidly produce

IL-4 | IFN-y

How are NK-T cells triggered to produce cytokines

Lipid and CD1 dependent fashion

NK-T cells regulate what immune response

Adaptive immune response

How do NK-T cells regulate adaptive immune response

Secreting cytokines

What is the major physiological function of immune responses to pathogens

Protect the host against microbial infection

Protecting the host against microbial infection is the major physiologic function of what

immune responses to pathogens

Pathogens include

Bacteria Viruses Parasites Yeast

Immune response to pathogens is mediated by combined effector mechanisms of ____ and ____

innate and adaptive immunity

T/F Immune responses to pathogens -respons in distinct and specialized ways to different types of microbes

True

Microbe survival and pathogenicity in a host are influenced by

Ability of the microbe to evade or resist effector mechanisms of immunity

Ability of microbe to evade or resist effector mechanisms of immunity =

Microbe survival and pathogenicity

T/F some pathogens require intervention to eradicate

True

T/F Tissue injury and disease may be cased by the host response to the microbe

True

Responses to Bacterial Infection uses which 2 systems

Innate immunity | Adaptive immunity

Innate immunity includes

Complement system Natural antibodies Phagocytes Acute phase proteins

All of these are part of what immunity Complement system Natural antibodies Phagocytes Acute phase proteins

Innate Immunity

Alternate and Lectin are what part of the innate immunity

Complement system

``` Nitric Oxide Myeloperoxidase Lysozyme Defensins are all ```

Phagocytes

Phagocytes of innate immunity are

Nitric Oxide Myeloperoxidase Lysozyme Defensins

Adaptive immunity -B cell/NK cell includes

Complement system Antigen specific antibodies ADCC

These are all part of what immunity Complement system Antigen-specific antibodies ADCC

Adaptive B cell/NK cell

Classical is what part of the adaptive immunity

Complement system

ADCC includes which 2 cells

NK cells | Eosinophils

NK cells and Eosinophils make up which part of the adaptive immunity

ADCC

Adaptive immunity of T cells includes

CD4+ TH IFN-y secretion CD8+ CTLs CD4+ TH17 activation

These are all part of what immunity CD4+ TH IFN-y secretion CD8+ CTLs CD4+ TH17 activation

Adaptive T cells

Macrophage activation is what part of adaptive immunity

CD4+ TH IFN-y secretion

CD4+ TH IFN-y secretion causes

macrophage activation

Killing cell infected with intracellular bacteria is what part of adaptive immunity

CD8+ CTLs

CD8+ CTLs cause

Killing cell infected with intracellular bacteria

CD4+ TH17 activation causes

IL-17 secretion

IL-17 secretion is what part of adaptive immunity

CD4+ TH17 activation

Function of IL-17 secretion

Recruit Neutrophils | Anti-microbial peptides

Recruitment of Neutrophils and Anti-Microbial peptides come from

IL-17 secretion

Examples of extracellular bacteria

Salmonella Staphylococcus aureus E coli

Salmonella Staphylococcus aureus E coli are all what

Extracellular bacteria

Complement activation leads to what outcomes

Phagocytosis of C3b coated bacteria Inflammation Lysis of microbe

Phagocytosis of C3b coated bacteria Inflammation Lysis of microbe are due to what part of antibody responses to extracellular bacteria

Complement activation

Antibody in antibody responses to extracellular bacteria leads to what outcomes

Neutralization | Opsonization and Fc receptor mediated phagocytosis

Neutralization Opsonization and Fc receptor mediated phagocytosis is due to what part of antibody responses to extracellular bacteria

Antibody

Response looks like Bacteria B cell Helper T cells for protein antigens ?

Antibody

Which part of antibody responses to extracellular bacteria can branch off into complement activation

antibody

T cell responses to extracellular bacteria looks like Bacteria DC Presentation of protein antigens ?

CD4+ helper cell

CD4+ helper cell leads to these factors

IL-17, TNF, other cytokines IFN-y Various cytokines

IL-17, TNF and other cytokines cause what response

Inflammation

IFN-y cause what response

Macrophage activation | Phagocytosis and bacterial killing

Various cytokines cause what response

Antibody response

Inflammation is due to what factors

IL-17, TNF, other cytokines

Macrophage activation | Phagocytosis and bacterial killing is due to what factors

IFN-y

Antibody response is due to what factors

Various cytokines

Synergistic Anti-bacterial Immune Mechanism involves which 3 immunities

Innate Cell-Mediated Antibody-mediated

Antibody mediated immunty has antibodies which do what

Opsonization | Toxin neutralization

Innate Immunity has Defensins and Lysozyme which cause

Lysis | Toxin neutralization

Innate Immunity has Complement which does what

Lysis Opsonization Toxin neutralization

Cell mediated immunity has activated macrophages which cause

Toxin neutralization

Cell mediated immunity has T cells and NK cells which cause

Cell mediated cytotoxicity | Toxin neutralization

Examples of intracellular bacteria

Brucella abortus Mycobacterium sp Ehrlichia canis

Brucella abortus Mycobacterium sp Ehrlichia canis are all examples of

Intracellular bacteria

What bacteria are facultative, intracellular organism

Brucella

What bacteria are nonmotile, nonsporing, rod shaped, gram negative coccobacilli

Brucella

Brucella Abortus is what species

Cattle

Brucella Melitensis is what species

Sheep | Goat

Brucella Suis is what species

Swine

Brucella Canis is what species

Canine

Innate immunity is during which days of infection

0-7

Adaptive immunity is during which days of infection

7-14

Innate immunity includes which cells

NK cells Neutrophils Macrophages

Innate immunity uses what factors

IL-12 | IFN-y

Adaptive immunity includes which cells

T cells | Macrophages

Adaptive immunity uses what factors

CD40L | IFN-y

Adaptive immunity causes

Eradication of ingection

Intracellular microbes include

Bacteria Virus Protozoa

Bacteria Virus Protozoa are all what

Intracellular Microbes

Immunity to Intracellular Microbes causes what 2 effects

Killing of bacteria in phagolysosome | Killing of infected cell

CTL=

Cytotoxic T cells

Immunity to Intracellular microbes includes which cells

CD4+ T cell | CD8+ CTL

Immunity to intracellular microbes uses which factor

IFN-y

CTL lysis of infected cell involves intracellular

Bacteria Viruses Protozoa

Infected cells degrade _____ into _____

intracellular pathogen | Peptides

Peptides are loaded into MHC I and presented to

cytotoxic T cells

Cytotoxic T cells induce

apoptosis and/or lysis of the cell

Cytotoxic T cell has what 2 factors

Perforin | Granzymes

Mechanism of immune evasion of extracelluar bacteria

Antigenic variation Inhibition of complement activation Resistance to phagocytosis Scavenging of reactive oxygen intermediates

``` Antigenic variation Inhibition of complement activation Resistance to phagocytosis Scavening of reactive oxygen intermediates are all mechanisms of ```

Immune evasion by bacteria

Antigenic variation Ex.

Neisseria gonorrhoeae Escherichia coli Salmonella typhimurium

Inhibition of complement activation Ex.

Many bacteria

Resistance to phagocytosis Ex.

pneumococcus

Scavenging of reactive oxygen intermediates Ex.

Catalase-positive staphylococci

Resistance to complement activation (alternative pathway) Ex.

Neisseria meningitides | Streptococcus

Sialic acid expression inhibits C3 and C5 convertase is a mechanism for what organism

Neisseria meningitides

M protein blocks C3 binds to organism, and C3b binding to complement receptors is a mechanism for what organism

Streptococcus

Toxin production Disruption of phagosome membrane, escape into cytoplasm Inactivation of reactive oxygen and nitrogen species Inhibition of pahgolysosome formation Decrease MHC II expression Super antigen production Polysaccharide capsule are all part of what mechanism

Immune evasion by bacteria

Toxin production is done by

LPS

LPS causes what

cell destruction and shock

Disruption of phagosome membrane, escape into cytoplasm is done by

Listeria monocytogenes (hemolysin protein)

Listeria monocytogenes causes what

disruption of phagosome membrane and escape into the cytoplasm

Inactivation of reactive oxygen and nitrogen species is done by

Mycobacterium leprae (phenolic glycolipid)

Mycobacterium leprae causes what

Inactivation of reactive oxygen and nitrogen species

Inhibition of phagolysosome formation is done by

Mycobacterium tuberculosis | Legionella pneumophilia

Mycobacterium tuberculosis and Legionella pneumophilia causes what

Inhibition of phagolysosome formation

Super antigen production done by

S. aureus toxin

Polysaccharide capsule causes

shield/shedding

Mechanisms of immune evasion by bacteria causes decreased

MHC II expression

Staphylococcus aureus Staphylococcal toxic shock syndrome toxin Th cell =

overproduction of IL-2 and IFN-y

Overproduction of IL-2 and IFN-y causes secondary overproduction of

IL-1 andTNF-a

``` IFN-a/B [Type I Inferons] NK cells Complement system Natural antibodies Activated Macrophages are part of innate or adaptive immunity ```

Innate

``` Virus specific antibodies Neutralization Opsonization Complement [Classical] ADCC -NK cells CTLs are part of innate or adaptive immunity ```

Adaptive immunity

NK cells IFN a/B Is high in innate or adaptive immunity

Innate immunity

Virus specific CTL Antibody is high in innate or adaptive immunity

Adaptive immunity `

Big switch on day __ between innate and adaptive immunity

IFNa/B induce expression of Adenylate synthetase Activate RNase L Degrades viral RNA This is the actions of

Biological actions of IFNa/B

Degrading viral RNA =

inhibit viral replication

Biological actions of IFN a/B

IFNa/B induce expression of Adenylate synthetase Activate RNase L Degrades viral RNA

Expression of enzymes that block viral replication PKR 16: 2'5' oligoadenylate synthetase RNase L18 is found in (uninfected/infected) cells

Uninfected

Uninfected cells lead to what state

antiviral state

Expression of molecules that enhance susceptibility to CTL mediated killing (Class I MHC) is found in (uninfected/infected) cells

Infected

infected cells lead to what

CTL killing of infected cell

When inhibitory receptor against viruses is engaged NK cell is (activated/not activated)

not activated | =no cell killing

Inhibitory receptor not engaged, NK cell is (activated/not activated)

Activated | =killing of infected cell

Activation of NK cells =

Killing of infected cell

When NK cells are not activated =

no cell killing

Virus inhibits class I MHC expression causing

Inhibitory receptor not to be in contact with normal cell

Inhibitory receptors engaged appear (early/late) in infections

Early

When NK cells kill they kill what kind of cells

viral infected cells and tumor cells

Immune responses against viruses uses what cells

NK cells

Immune responses against viruses uses which secretes what

IFN-y

When IFN-y is secreted it activates

Monocytes

Main goal of adaptive immunity

Protection against infection

Adaptive immunity includes what components

B cell | Antibody

Antibody neutralization is found in which immunity

adaptive immunity

CD8+ CTL combined with an infected cell causes

Killing of infected cell

When infected cell is killed what happens to infection

Eradication

ADCC causes killing of

antibody coated cell

IgG of the antibody coated cell interacts with low affinity FCyRIII on what cell

NK cell

Genetic recombination is seen in what virus

Influenza virus

What influenza's are combine to create Influenza A (H1N1)

Swine influenza NA AVian influenza Human (H3N2) influenza Eurasian Avian/Swine influenza

influenza virus has how many RNA segment genome

Mechanisms of Immune Evasion by Viruses causes inhibition of

Antigen processing and presentation

MHC down regulation causes

escape surveillance/presentation

Epitope mutation causes

Antigenic variation/immune escape | REduced/Failure of MHC loading

Antigenic variation/immune escape Reduced/Failure of MHC loading causes

epitope mutation

Inhibition of proteasomal activity Ex.

EBV | human CMV

Block in TAP transport:

HSV

Block in MHC synthesis and/or ER retention:

Adenovirus | human CMV

Removal of class I from ER

CMV

Interference with CTL recognition by decoy viral class I like molecules

murine CMV

Antigenic variation Inhibition of antigen processing - Blockade of TAP transporter - Removal of class I molecules from the ER Production of cytokine receptor homologs Production of immunosuppressive cytokine Infection of immunocompetent cells are all mechanisms of

Immune evasion by viruses

Antigen variation Ex:

Influenza Rhinovirus HIV

Blockade of TAP transporter

Herpes simplex

Removal of class I molecules from the ER

Cytomegalovirus

Production of cytokines receptor homologs

Vaccinia Poxaviruses (IL-1, IFN-g) Cytomegalovirus (chemokine)

Production of immunosuppressive cytokine

Epstein-Barr virus (IL-10)

Infection of immunocompetent cells

HIV

Latency integration into host genome is seen in

oncogenes

Feline Immunodeficiency Virus infects what cells

CD4+ T cells

Feline Immunodeficiency Virus causes slow destruction of

adaptive immunity

Diagnosis of Feline Immunodeficiency Virus

Presence of anti-FIV antibodies via western blot, ELISA or IFA

Clinical symptoms of FIV

Chronic inflammation Infection Weight loss Fever

Prevention of FIV

Vaccine

Tinea sp. is known as

Ringworm

Ringworm occurs due to failure of

immune clearance = persistent inflammation

_____ immunity is required to protect against fungal infections

Cell-mediated

Activated Macrophages, Neutrophils PRR-PAMP interaction Complement system are all part of (innate/adaptive) immunity

Innate

Utilize PRR-PAMPS: Phagocytosis is due to which part of innate immunity

Activated Macrophages, Neutrophils

Inflammation Neutrophil recruitment is due to which part of innate immunity

PRR-PAMP interaction

Lectin and Alternate pathways | due to which part of innate immunity

Complement system

Cell mediated clearance | Injurious effect of immune response are part of which immunity

Adaptive

CD4+ TH1 and TH17 cells are due to whcih part of adaptive immunity

Cell mediated clearance

Macrophages and neutrophil activation occur because of which cells

CD4+ TH1 and TH17 cells

Granuloma and fibrosis (Histoplasma capsulatum) are due to which part of adaptive immunity

Injurious effect of immune response

T/F some fungal cells are too large to be phagocytosed

Truse

Mechanisms of Immune Evasion by Fungi express complement and ______ inhibitors

reactive oxygen

Escape from phagosome/alter phagolysosome allows the fungus to

avoid destruction

Cryptococcus neoformans functions to

Inhibit TNF and IL-12 production | Stimulate IL-10 production

Fungi have complex ____coat

glycan

Phagosome maturation has 3 pathways 1. Killing 2. Non-lytic expulsion 3. Escape Which occurs in Fungal Evasion

Escape

Immune Responses to Helminths are ___dependent Eosinophil Degranulation

IgE

Cell mediated clearance causes

Activated CD4+ TH2 cells | Vulnerable Helminths

Activated CD4+ TH2 cells induce

Mucosal eosinophil and mast cells | IgE production

Mucosal eosinophil and mast cells IgE production are due to activation of what cells

CD4+ TH2 cells

Helminths are vulnerable to

ADCC involving eosinophils, neutrophils, and macrophages

ADCC involving eosinophils, neutrophils and macrophages | are stronger than

Helminths

Eosinophil degranulation releases

``` MBP ECP EP EN Phospholipase D Lysophospholipase ```

``` MBP ECP EP EN Phospholipase D Lysophospholipase are due to release of ```

Eosinophil degranulation

Release of MBP, ECP, EP, EN, Phospholipase D, and Lysophospholipase are toxi to

helminths

MBP

Major basic protein

ECP

Eosinophil cationic protein

Eosinophil peroxidase

Eosinophil neurotoxin

Protozoa immune responses

plasmodium species Leishmania donovani Trypanosoma brucei Entamoeba histolytica

``` Plasmodium species Leishmania donovani Trypanosoma brucei Entamoeba histolytica are what type of immune responses against parasites (protozoa, metazoa) ```

Protozoa

Metazoa immune responses

Schistosoma species | Filiaria (Wuchereria bancrofti)

Schistosome species Filiaria are what types of immune responses against parasites

Metazoa

Plasmodium species

Milaria

Protective mechanisms against Milaria

Antibodies and CD8+ CTLs

Leishmania donovani

Leishmaniasis (mucocutaneous, disseminated)

Protective mechanisms against Leishmaniasis

CD4+ TH1 cells activate macrophages to kill phagocytosed parasites

Trypanosoma brucei

African trpanosomiasis

Protective mechanisms against African trpanosomiasis

Antibodies

Entamoeba histolytica

Amebiasis

Protective mechanisms against Amebiasis

Antibodies | Phagocytosis

Schistosoma species

Schistosomiasis

Protective mechanisms against Schistosomiasis

ADCC mediated by eosinophils, macrophages

Filaria

Filariasis

Protective mechanisms against Filariasis

Cell mediated immunity | role of antibodies

Mechanisms of Immune Evasion by Parasites

Antigenic variation Acquired resistance to complement, CTLs Inhibition of host immune responses Antigen shedding

``` Antigenic variation Acquired resistance to complement, CTLs Inhibition of host immune responses Antigen shedding are all mechanisms of ```

Immune Evasion by Parasites

Antigenic variation

Trypanosomes | Plasmodium

Acquired resistance to complement, CTLs

Schistosomes

Inhibition of host immune responses

Filaria (secondary to lymphatic obstruction) | Trypanosomes

Antigen shedding

Entamoeba

Immunization routes

SubQ or IM

Antigen drains to the nearest

lymph node

what immunity does antigen stimulate

systemic immunity

Antigen draining to the nearest lymph node does NOT stimulate

mucosal immunity

``` Prescapular (superficial cervical) Axillary Femoral Popliteal Superfical inguinal Iliac Submandibularis Retropharyngeal Facial are all ```

Peripheral immune system draining into lymph nodes

Innate protection mechanisms on body surface : Eyes

Tears | blinking

Innate protection mechanisms on body surface: Nose

Turbulence | Sneezing

Innate protection mechanisms on body surface: Mouth

Vomiting | Saliva

Innate protection mechanisms on body surface: Esophagus/Trachea

Mucus Cilia Coughing

Innate protection mechanisms on body surface: Stomach

Acid pH | Vomiting

Innate protection mechanisms on body surface: Intestines

``` Normal flora Anaerobiasis Lysozyme Defensins Proteases Diarrhea ```

Innate protection mechanisms on body surface: Back

Dessication Desequamation Fatty acids Normal flora

MALT

Mucosa Associated Lymphoid Tissues

MALT cellular mass (exceeds/underscores) total lymphoid cells in bone marrow, thymus, spleen and lymph nodes

Exceeds

MALT is found in what organs

Bone Marrow Thymus Spleen Lymph nodes

NALT

Nasal associated lymphoid tissue

Ex of NALT

Tonsils

GALT

Gut associated lymphoid tissue

Ex of GALT

Peyer's patches

BALT

Bronchus associated lymphoid tissue

Large lymphoid areas are continuously exposed to

microorganisms and food antigens

Large lymphoid areas have _______ largest organ

Mucous membrane

Large lymphoid areas are partially separate from ____ immune system

peripheral

Epithelial barrier = _____immunity

innate

Large lymphoid areas produces T and B cell effectors and memory cells which are generated in 1 location then

circulate to distant sites

Large lymphoid areas of MALT provide tolerance to

food antigens

Epithelial Barrier Immune Functions

Epithelial Tight junctions

Mucus includes

Mucins Lipids Bicarbonate fluid

Mucus is secreted by

Goblet cells

Mucus has ____ pH at epithelial layer

Neutral

Mucus adheres to luminal surface of epithelium allowing ____ to pass but not ____

Nutrients | Macromolecules

Defensins are

antimicrobial peptides

defensins are secreted by

paneth cells

defensins do what to bacterial membranes

disrupt

Epithelial cells produce ____ and | ____

cytokines | chemokines

IL-10 and TGF-B serve what function

immunosuppressive

TNF a allows

TH1 differentiation

CXCL1 for what cells

Neutrophils

CCL2 for what cells

Eosinophils

CXCL10 for what cells

lymphoctes

Compartments of MALT

Inductive sites | Effector sites

Antigen is processed and T and B cells are activated Ab class switching occurs in which site of MALT

Inductive site

Sites where antibody and cell mediated responses are generated against pathogens

Effector sites

Effector sites are (close/distant) from inductive sites

Distant

Antibody is released by what cells

Plasma cells

CTLs kill what cells

virus infected cells

CTLs and Antibody are found at which site

Effector site

Ab class switching occurs at which site

Inductive site

``` Tonsils NALT BALT Appendix Peyer's patches are all part of which site ```

Inductive site

Most mammals except rodents have

tonsils

NALT

pharynx, nasal lymphoid tissue

Peyer's patches are discrete in

jejunum

Antigen Transport Across Mucosal Epithelium occurs by 2 cells

M cells | Intestinal Mucosa DCs

Discrete Peyer's Patches in jejunum have 3 regions

Dome region Germinal center Parafollicular region

Dome region Germinal center Parafollicular region are all regions of

Peyer's patches in jejunum

In Peyer's Patches in jejunum-antigen transfer is done by what cells

M cells

CD4 T cells, DCs, macrophages are part of what region

Dome region

Dome region has what cells

CD4 T cells DCs Macrophages

B cells, class switching are part of what region

Germinal center

Germinal center has what cells

B cells | Class switching

CD4, CD8, DCs, macrophages are part of what region

Parafollicular region

Parafollicular region have what cells

CD4 CD8 DCs Macrophages

T cell differentiation occurs in what sites

Inductive sites

DC cells give rise to what factors

IL-10/TGF-B IL-4 IL-12 IL-23

Low dose antigen food gives rise to what cell

Treg

Extracellular pathogen parasites give rise to what cell

Th2

Intracellular pathogen give rise to what cell

Th1

Endogenous flora give rise to what cell

Th17

IL-10/TGF-B Treg Gives rise to what factors

IL-10 | TGF-B

IL-4 Th2 Gives rise to what factors

IL-4 IL-5 IL-10

IL-12 Th1 Gives rise to what factors

IFN-y

IL-23 Th17 gives rise to what factors

IL-17 | IL-6

Homing Properties of Intestinal lymphocytes uses what effectors

CD4 CTL B cells

Chemokines cause direct homing of _____

effector lymphocytes

Main mucosal Ig in most animal species

Secretory IgA

What is the most important mucosal Ig in Cattle which are the exception

IgG

T-dependent IgA class switching occurs where

In the gut

T-independent IgA class switching occurs where

In the gut

APRIL

A Proliferation Inducing Ligand

Transport of IgA across epithelial cells occurs in which 3 areas

Lamina propria Mucosal epithelial cell Lumen

Where do these reside IgA-producing plasma cell J chain Dimeric IgA Poly-Ig receptor with bound IgA

Lamina propria

Where do these reside Endocytosed complex of IgA and poly-Ig receptor

Mucosal epithelial cell | Proteolytic cleavage

where do these reside Secreted IgA

Lumen

Intestinal Villi Components

IEL yST cells CD8+ aB T cells

IEL

Intraepithelial lymphocytes

what cells are in the lamina propria of villi

CD4 T cells

what cells are in the LPL of villi

B cells

LPL

Lymphocytes

Crypt epithelium-Paneth cells use what enzymes

lysozyme | Defensins

yS TCR or aB TCR Thymus independent

yS or aB Not classical MHC restricted (use CD1)

yS or aB epithelial surveillance

yS or aB epithelial differentiation

yS or aB cytolytic

yS or aB requires epithelial APC

yS or aB thymis dependent

yS or aB MHC I restricted

yS or aB Primed in Peyer's Patches

yS or aB Home to epithelium

yS or aB cytolytic

yS or aB Requires Dendritic APC

Parasite antigens prime what cells

Th2

When Th2 are primed it produces what factor

IL-4

IL-4 activates what cells

B cells

When IL-4 activates B cells it causes a class switch to

IgE | some IgG is made and can bind and activate complement

IgE is released from what cells

plasma cells

IgE binds ____ receptor on mast cells

IgE recognizes ____ produced by worm

antigen

Mast cells ____

degranulate

Histamine/serotonin release = (increase/decreased) vascular permeability

increased

_____ contraction leads to worm detachment and elimination with bowel contents

Smooth muscle

IL-5 attracts what cells

eosinophils

What do eosinophils do to parasites

paralyze or kill

Major basic protein of eosinophil effector molecules damages ___

cuticle

ADCC of parasites by eosinophils = eosinophilic ____

neurotoxin

Eosinophilic peroxidase does what

oxidizes

Eosinophils have Fc receptors that bind to ___

antibody coated parasites | ADCC

ADCC

Antibody dependent cell cytotoxicity

Functions of Tregs at Mucosal Surfaces (upregulate/inhibit) the whole pathway of Treg, Th2, Th1, Th17

Inhibit

Exam 2 Flashcards

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