Immunology Exam 2 Review

Reminder for Merc: review complement and add more cards

What is hematopoiesis?

Formation of blood cellular components

What are pluripotent stem cells? What’s an example?

Stem cells that can differentiate into many blood cell types. Ex: Hematopoietic stem cells

Describe PAMPs

Evolutionarily conserved molecular motifs, specific to particular microbes

Ex: peptidoglycan, Gram-negative LPS, dsRNA

Describe the characteristics of innate immune response. (How fast is it? What does it target?)

Immediate

Non-specific

Not enhanced by multiple exposures

What is primary ciliary dyskinesia?

Cilia in the nasal cavity, respiratory tract, and inner ear are malformed, resulting in impaired mucociliary clearance.

Clinical signs: infections within a few weeks of birth. Recurrent bacterial rhinosinusitis and bronchopneumonia.

Old English Sheepdogs, English Springer Spaniels, Newfoundland, Dachshund, Irish Wolfhound, Staffordshire Bull-terrier

What is the primary function of sentinel cells? Where in the body are they most common?

To recognize and respond to invading microbes. Present in highest number just below body surfaces.

What are three examples of sentinel cells?

Macrophages, dendritic cells, and mast cells.

Name two professional phagocytes.

Neutrophils

Macrophages

What two cell types can phagocytose as a secondary function? (Not professional phagocytes)

Eosinophils

Basophils

What cells are involved in the cellular branch of innate immunity?

Neutrophils

Macrophages

Mast Cells

Lymphoid cells

Basophils

Eosinophils

What components are involved in the humoral branch of innate immunity?

Complement system

Natural antibodies

Acute-phase proteins

Antimicrobial peptides

Soluable lectins

Following phagocytosis, what two distinct processes do neutrophils use to destroy microbes?

Respiratory burst, and the use of lytic enzymes and other antimicrobial compounds in neutrophil granules.

How does respiratory burst work?

Binding of bacteria allows NADPH-oxidase (NOX) to assemble and generate singlet oxygen (free radicals). Singlet oxygen interacts w/ water to produce hydrogen peroxide and chloride ions, creating hypochlorite (bleach).

What is an additional method of microbial control that neutrophils use to “catch and kill” microbes?

Neutrophil Extracellular Traps (NETs)

What do NETs consist of?

Sticky DNA containing antimicrobial molecules.

What are some of the functions of macrophages?

Kill bacteria that defeat neutrophils

Trigger tissue repair and wound healing.

Where are macrophages located? Where do they mainly originate?

In tissues and bloodstream. Generally come from the bone marrow.

What is the specialized tissue macrophage of the liver?

Kupffer cells

What is the specialized tissue macrophage of the lungs?

Alveolar macrophages, intravascular macrophages

What is the specialized tissue macrophage of the brain?

Microglial cells

What is the specialized tissue macrophage of connective tissue?

Histiocytes

What is the specialized tissue macrophage of the blood?

Monocytes

What are the two types of macrophages?

M1 and M2

What is the function of M1 macrophages?

They are aggressively phagocytic, secreting proinflammatory cytokines and loaded with nitric oxide synthase and proteases.

Activated in a way that enhances their destructive abilities

What is the function of M2 macrophages?

Trigger wound repair and healing by secreting anti-inflammatory cytokines.

What are some of the cytokines produced by macrophages?

IL-1, IL-23, TNF-alpha, IL-18, IL-12, IL-6

In humans, mice, and dogs, most particulate material is removed from the bloodstream by what type of cells in the liver?

Kupffer

In horses, pigs, and cats, particulate matter is removed by intravascular macrophages in what organ?

The lungs

What causes Chediak-Higashi Syndrome?

Autosomal recessive gene mutation in the lysosomal trafficking regulator (LYST, aka CHS1). This causes neutrophils to be unable to digest and kill microbes.

What changes occur in neutrophils in Chediak-Higashi Syndrome? What is the consequence?

Giant lysosomal granules develop in the cytosol, which cannot fuse w/ phagosomes.

What clinical signs are associated with Chediak-Higashi Syndrome? In which animals is it most common?

Neutrophil/platelet abnormalities, shortened lifespan, dilution of melanin, recurrent bacterial respiratory infections, and oculocutaneous albinism. Common in some cat and cattle breeds.

Specific ex: Blue smoke color Persian cats

How do we treat Chediak-Higashi Syndrome?

symptomatically

What are the two pathways in the complement system?

Classical and alternate

What compound is important in both the classical and alternate pathways of the complement system?

C3 convertase

What is opsonization?

Bacteria cannot easily be captured alone due to their surface charge, so it can be coated by antibodies, or complement bodies can bind to their neutrophil receptors to make them more easily ingestible.

What is the importance of cell adhesion molecules (CAMs)? What are a few examples?

They help neutrophils migrate to sites of infection.

Ex: selectins, GlyCAM-1, MAdCAM-1, etc.

What about vessels changes in inflamed tissues, allowing neutrophils to leave the bloodstream?

In healthy vessels, neutrophils bounce off the walls and continue through circulation. In inflamed tissues, blood vessel walls become sticky. Neutrophils stick to the vascular endothelium, which is mediated by integrins and selectins.

Failure to terminate acute inflammation causes what?

Chronic inflammation and tissue destruction

What is resolution (in the context of acute inflammation)?

Active termination of inflammation, coordinated within hours of starting an inflammatory response.

What are the mechanisms of acute inflammation resolution?

Inflammatory mediators have a short life in vivo (C3a, PG)

Production of anti-inflammatory cytokines (like IL-10 and TGF-beta)

Apoptosis of pro-inflammatory cells (like neutrophils)

Desensitization (PG receptors)

How does adaptive immunity develop?

Upon foreign antigenic stimulation (exposure to pathogen/foreign material)

What is different about adaptive immunity from innate?

Development takes time (days to weeks)

Specific to each foreign antigen

Has memory

Effectiveness increases upon repeated exposure

What is the difference between primary and secondary response (adaptive immunity)?

Secondary includes IgM to IgG/IgA isotype switching, affinity maturation, and a shorter lag time due to memory.

What is an example of a cell-mediated adaptive response?

Foreign organ graft rejection: body senses cells are different than those of the recipient and rejects the graft.

What are cytokines?

Proteins secreted by cells of the immune system, whose function is to regulate immune response by communication amongst cells.

What are three ways cytokines exert their effects? (Hint: “-crine”)

Autocrine, paracrine, and endocrine

What is the term when a protein acts on adjacent cells?

Paracrine

What is the term when a protein acts on a cell that produced it?

Autocrine

What is the term when a protein acts on cells in distant locations?

Endocrine

What are the general properties of cytokines?

1. Mediate and regulate immune response/inflammation

2. Not pre-formed. Synthesized for a short period.

3. Influence production of other cytokines

4. Can act on many cell types and produce different responses (pleiotropy)

5. Many cytokine may act on one cell type to produce one type of response (redundancy)

During what phase of innate and adaptive immune responses are cytokines produced?

Effector phases

What are the major differences between hormones and cytokines?

Hormones are made by specific cells in the endocrine system, whereas cytokines are made by many cell types. Hormones are not redundant or pleiotropic like cytokines. Hormones only provide endocrine effect, while cytokines can be endo/auto/paracrine.

Hormones function in maintaining homeostasis in the body, while cytokines play roles in inflammation, immune response, and tissue repair.

What are some examples of cytokines (broad categories)?

Interleukins

Interferons

Tumor necrosis factor

Growth factors

Chemokines

What do interleukins do?

Regulate interactions between lymphocytes and other leukocytes

What do interferons do?

Anti-viral function, produced in response to viral infection and other immune stimulation

What does tumor necrosis factor do?

Immune function and anti-tumor activity

What do growth factors do?

Regulate stem cell growth, hematopoiesis

What do chemokines do?

Chemotaxis of immune cells

What is chemokine nomenclature based off of?

Their structure

What does Birnavirus (Gumboro disease) affect?

The Bursa of Fabricius; causes lymphoid depletion and inflammation of the bursa

What are the three major types of antigen presenting cells (APCs)?

Dendritic cells

Macrophages

B-cells

AKA Professional APCs!

What is the role of dendritic cells?

Best antigen presenting cell, activates all states of T-cells, including naive T-cells

What is the function of B-cells?

Excellent at presenting soluble protein Ag present in low concentrations to non-naive T-cells

What are macrophages good at in the context of antigen presentation?

They are good at presenting particulate antigens to non-naive T-cells

What two major structures do antigen presenting cells have?

MHC I and II

Co-stimulatory molecules (CD40)

What creates the best antigens/immunogens?

1. Molecular size: The bigger the better. Ideally >20,000 kDa

2. Chemical nature/composition: Complex and organic molecules are more antigenic.

3. Stability: Stable is better

4. Physical form: Particulate antigens are more immunogenic than soluable antigens. Denatured are also more immunogenic than native form.

5. Foreignness: The greater the difference between antigen and host, the stronger the response.

6. Degradability: Antigens that are easily phagocytosed/degraded are more immunogenic.

What are linear epitopes?

Structures of an antigen recognized by an antibody, BCR, or TCR that are composed of a single linear segment of a polypeptide chain.

What is a conformational epitope?

Structures of an antigen recognized by an antibody that are composed of a 3-dimentional polypeptide structure. More likely to occur in nature than a linear epitope. NOT recognized by TCR. (Recognized by Abs and BCR)

What are haptens?

Low molecular weight compounds that cannot elicit an immune response alone, and so are bound to a larger molecule (creating an artificial epitope).

What are the five classes of immunoglobulins?

IgM, IgG, IgA, IgE, and IgD

Briefly describe antibody structure?

Two identical light chains, two identical heavy chains, linked by disulfide bonds

How do light chain variable regions (V_L) vary between antibodies?

Antibodies from different B cells/plasma cells have different V_L, but antibodies from the same B cells or daughter B cells have identical V_L.

How do light chain constant regions (C_L) vary between antibodies?

Only on kappa or lambda light chains. Antibodies from the same animal have very similar C_L based on isotype.

How do heavy chain variable regions (V_H) vary between antibodies?

Antibodies from different B cells/plasma cells have very different V_H, but antibodies from the same B cells or daughter B cells have identical V_H. This is needed for antigen specificity.

How do heavy chain constant regions (C_H) vary between antibodies?

Antibodies from the same animal or even species have very similar C_H. There are five major isotypes and several additional isotype subtypes of C_H.

Cell-bound B-cell receptors have a membrane-binding domain. What must happen for antibodies to be released into the bloodstream?

The membrane-binding exon CmM is excised and replaced by a secreted CmS exon.

What is the difference in antigens of MHC Class I and II T-cells?

MHC Class 1: Antigen is small peptide (8-12 amino acids long). Binds the groove only at the ends.

MHC Class 2: Antigen is longer (12-40 amino acids long). Binding residues are along the length of the groove.

How does MHC diversity arise?

MHC loci are highly polymorphic (many alternative forms of the gene/allele are present).

Polygeny: recombination between different genes

Codominance: heterozygote advantage

What is the function of the BCR complex?

Antigen recognition and binding. Can recognize large complex molecules.

What is the purpose of CD79?

Signaling to the cell

How are B-cells stimulated?

1. Antigen binds

2. T-cells help

3. Complement helps

4. Toll-like receptors and PAMP help

During B-cell stimulation, how does the complement system help?

It reduces the threshold of B-cell activation by 100 times.

Complement product C3d and BCR CD21 is produced, followed by signal transduction through CD19.

In B-cell stimulation, how do toll-like receptors and PAMP help?

B-cell stimulating ligands include LPS, flagellins, CpG DNA, etc.

How do T-cells aid in B-cell stimulation?

1. Ag binds to TCR, causing cell to express CD154 (aka CD40L)

2. CD154 binds to CD40 on the B cell, promoting Ig synthesis and CD86 (B7) expression on the B cell

3. CD86 binds to CD28 on the T cell and triggers IL-4 (and other Th2 cytokines) production.

4. IL-4 promotes B cell growth and differentiation (additional signal)

What are the characteristics of T-independent antigens?

1. Simple repeating polymers (LPS, flagellins, capsular polysaccharides, etc.)

2. They bind directly to BCRs and crosslink several BCRs

3. Trigger only IgM

4. Do not generate memory cells

What is somatic mutation of B-cells? Where does it occur?

Type of B-cell processing: B cells are selected based on their affinity for antigen. It only occurs in germinal centers.

What are plasma cells? What can they do?

Terminally differentiated B cells.

Can generate thousands of immunoglobulin molecules per second. Not usually long-lived. May become cancerous (myelomas).

Antigens binding to the BCR signals the B cell to what?

Divide

Differentiate into plasma and memory cells

Secrete antibodies

Immunoglobulins can be membrane bound as a part of ___, or secreted as ___ in blood, lymph, tissue spaces, and secretions.

B-cell receptor (BCR); antibodies

What are immunoglobulin domains? Where are they found?

They are specific structural arrangements of proteins (usually about 110 amino acids) that include an internal disulfide bond and two layers of beta-pleated sheets. They are used to construct proteins in the immunoglobulin superfamily. They are found on antibodies, TCRs, cell-adhesion molecules (CAMs), and co-receptors like CD4 and CD8.

In what types of cells are MHC Class I and II cells found?

Class I: Almost all enucleated cells in the body.

Class II: Professional antigen presenting cells

Does the arrangement of MHC differ between species?

Yep

What is MHC Class III?

NOT an antigen receptor or antigen presenting molecule.

Codes for immune proteins, complement proteins, stress proteins, steroid hormones, etc.

Endogenous antigen processing pathway involves what cell types? What kind of antigen?

All nucleated cells (MHC Class I)

Intracellular antigens (from viruses and other intracellular organisms).

Exogenous antigen processing pathway involves what cell types? What kind of antigen?

Only in antigen presenting cells (MHC Class II)

Extracellular antigens (from bacteria, fungus, protozoa, etc.)

What does it mean for T-cells to be MHC restricted?

T-cells only respond to antigen in the MHC-binding groove. They will not respond to free protein fragments (hence the need for antigen processing).

What is the function of CD79?

To send the signal to begin transcription after an antigen has bound to the BCR. This drives B-cell clonal proliferation and differentiation.

It is not sufficient by itself for full B-cell activation.

Native/linear epitopes are recognized only by what type of cells?

B-cells, not T-cells. T-cells recognize processed epitopes.

If plasma cells become cancerous, many B-cell clones cause what?

Multiple myeloma

What are the two T-cell subpopulatoins?

alpha-beta and gamma-delta