Veterinary Immunology Test 1

Variolation

controlled exposure

ex: infected people with pus from smallpox sores

effective, often deadly, spread the disease

practiced in the US 1700s

Vaccination

Edward Jenner: 1st to produce vaccine

used milkmaid cowpox infection against smallpox and challenged boy twice

did not spread smallpox, mild disease

Functions of the immune system

its a sensory & regulatory network

detects internal disruptions

eliminates pathogens

clears cellular debris

promotes tissue repair

tolerate self & maintain homeostasis

Bad aspects of immunity

allergic reactions, chronic inflammation, autoimmune disease

Innate Immunity

physical & chemical barriers (skin)

granulocytes (phagocytes/ blood cells that eat pathogens)

Complement

Antimicrobial peptides (tears, saliva)

NK cells

always present, act within seconds post injury

detection based on broad molecular patterns (Microbial associated molecular patterns, MAMPs)

Microbial Molecular pattern

present in microbes but not in host

ex: bacteria cell wall components, targeted bc not present in host

Key features of innate immunity

rapid response

pattern based recognition (PAMPS & DAMPS)

activates & shapes the adaptive response

Pattern recognition receptor (PRRs)

recognize PAMPS and DAMPS

Toll like receptors & Complement receptors

Describe adaptive immunity

B cells & T cells

activated by exposure

takes days to weeks

specific

memory

B cells receptor secrete __ when it finds its ligand antigen

an antibody or immunoglobulin

they bind to antigens in native state (recognize protein shape)

What do variable regions allow for in B & T cell receptors

allow for generation of different receptors to recognize more antigens

What do B & T cells recognize

B cells: proteins, carbs, lipids, nucelic acids

T cells: peptides (short amino acid/protein)

T cells only recognize short peptides and need what to do this

Dendritic Cells digest proteins & present it to them with a MHC carrier protein

What is an epitope

specific part of an antigen that is recognized by the immune system

How are lymphocyte antigen receptors created

antigenic epitope genetic recombination (lock, variable region)

BCR/B cells: stay in bone marrow (primary lymphoid ogran)

TCR/T cells: thymus (primary lymphoid organ)

Immunological Tolerance

suppression of self reactive lymphocytes are usually sufficient to avoid reactivity against self tissues

How will the small number of lymphocytes encounter antigens in large body

lymph nodes are located all around the body & places for antigen accumulation and lymphocyte migration ( increase chances of lymphocyte encountering corresponding antigen)

What happens when individual lymphocyte encounters target antigen

stops migrating, starts proliferating to create army response

afterwards portion of them die, portion of them retained as memory cells (fight off second infection)

T/F adaptive and innate immunity work together

true, innate present antigens to adaptive immune system

innate immunity is blank and blank; adaptive immunity is blank and blank

nonspecific & rapid

specific & slower

Name the primary lymphoid organs in mammals and birds

thymus, bone marrow, bursa of fabricius

Sort these into innate, adaptive, or both: neutrophil, macrophage, complement, B cell, T cell, antibody, dendritic cell.

innate: neutrophil, macrophage, complement, dendritic cell.   Adaptove: T cell, B cell, antibody 

What mechanism generates the enormous diversity of BCRs and TCRs?

The genetic recombination of the variable region/antigenic epitope

What do phagocytes do after recognizing a microbe? Name two major phagocytes.

Two major phagocytes are dendritic cells and granulocytes. Dendritic cells engulf a microbe and present them to T cells via a carrier protein (MHC)

define MAMP, PAMP, and DAMP in your own words. Then give one example of each.

MAMP is found in all microbes whether they cause disease or not. Ex: peptidoglycan 

PAMP is recognized as something on a microbe that can cause disease. Ex: bacterial cell wall 

DAMP is a signal that the bodies own cells are damaged. Ex: ATP leaking out of cell 

A sterile crush injury releases ATP; a bacterium provides peptidoglycan. Label each signal and predict whether both can cause inflammation.

Release of ATP is a DAMP. Bacteria providing peptidoglycan is a PAMP. Yes both signals cause inflammation.

Put these in order: peptide presentation, antigen capture, lymphocyte activation, antigen processing, clonal expansion.

1. Antigen capture 2. antigen processing 3. peptide presentation 4. lymphocyte activation 5. clonal expansion 

Explain the distinct jobs of lymph nodes, and of MHC molecules.

The role of the lymph nodes is to trap microbes from circulation and have T cells and B cells ready for response. The role of MHC molecules is to capture microbes, break them down, and present them to T cells for response. They also help determine self versus non self. 

A dog is vaccinated and later encounters the pathogen. Contrast the first and second adaptive responses.

Vaccination leads to a slow primary response that produces a small amount of antibodies. The secondary response is rapid because of memory cells and clears the pathogen much faster.

Where do immune system cells originate

primarily from hematopoietic stem cells in the bone marrow, that then decide to be myeloid progenitor (innate immune system) or lymphoid progenitor ( adaptive immunity)

during embryonic development: yolk sac → fetal liver/spleen → bone marrow

What controls hematopoietic stem cell survival and differentiation

hormones, cytokines, and growth factors through both paracrine and endocrine signaling

What are the three ways cells communicate using secreted mediators

autocrine: cell produces & gives to itself

paracrine: cell produces factor to nearby cell

endocrine: cell produces factor to circulation to distant cell

What is the primary function of neutrophils

segmented nuclei, short lived

rapid phagocytosis and killing of microbes through granules ( make up majority of wbc’s)

innate

what do neutrophil granules contain

antimicrobial peptides, lysozyme, and proteases used for intracellular kiling

what are eosinophils primarily involved in

Helminth/parasite (large pathogens) defense and allergic/hypersensitivity reactions

short lived

why are eosinophils effective against helminths

their granule proteins damage parasites that are too large to phagocytose

how do mast cells and basophils differ

mast cells = tissue resident

basophils = circulate in blood

what do mast cells and basophils have in common

both can degranulate and release histamine and other vasoactive mediators

promote acute inflammation & allergies

low in percentage

what are monocytes

immature circulating cells (macrophages) that migrate into TISSUES and differentiate

DCs migrate to peripheral tissues, osteoclasts, circulating monocytes: respond to inflammation

what is the major function of macrophages

phagocytosis after migrating into tissues

Match macrophages with their locations

Kupffer cells — liver
→ Microglia — brain/CNS
→ Osteoclasts — bone
→ Alveolar macrophages — lungs
→ Langerhans cells — epidermis
→ Histiocytes — connective tissue

What are the three major lymphocyte types

B cells, T cells, and natural killer cells (NK)

What are the two major types of T cells

CD4 T helper cells: orchestrate immune responses

CD8 cytotoxic T cells: kill target cells

What are the major T cell activation states

Naive (havent met antigen yet)→ activated/effector (proliferate, act)→ memory cells

What is the primary function of B cells

they are the lymphocyte lineage responsible for antibody production

what are the major B cell states

Naive → germinal center B cell (stay in lymph nodes)→ plasma cell (secrete antibody)→ memory cell

NK cells do what

detect stressed cells and trigger apoptosis (ex: if MHC is repressed and not shown they will kill that cell)

tumor defense

releases perforin and granzymes granules that make holes in target cell (kill)

what happens to primary lymphoid organs with age

bone marrow: red marrow is increasingly replaced by yellow marrow

thymus/bursa: involute with age and are replaced by adipocytes

what happens to production of new naive lymphocytes with age

highest in young animals and lowest in old animals

what is the thymus and where is it located

lobular gland in the cranial mediastinum where T cell precursors mature

what happens to T cells in the thymic cortex

immature T cells undergo positive selection- cells that recognize self MHC survive ( can you make TCR)

TOLERANCE

what happens in the thymic medulla

negative selection eliminates autoreactive T cells, promoting self tolerance

What percentage of developing thymocytes become naive T cells

2%

what are the secondary lymphoid organs/tissues

encapsulated: lymph nodes, spleen,

unencapsulated: MALT, and tonsils

what are examples of MALT

GALT, BALT, Peyer’s patches, and solitary lymphoid follicles

How does lymph flow through a lymph node

afferent vessels → lymph node → single efferent vessel

what are the major regions of a lymph node

cortex: B cell follicles (outer edges)

paracortex: T cell region

medulla: plasma cells/macrophages +lymphatic sinuses

what happens to B cell follicles during an active immune response

B cells proliferate, forming secondary follicles with germinal centers

they train BCRs at germinal centers

What is special about pig lymph nodes

they are essentially inside out; T cells are in cortex and B cells are in medulla

What are peyer’s patches

unencapsulated lymphoid aggregates in the gut (SI) with B cell rich follicles surrounded by T cells

What is MALT

Mucosa associated lymphoid tissue that protects mucosal surfaces and connects with the systemic immune system

ex: Intraepithelial lymphocytes search for infection in intestines

What are the two major areas of the spleen and their functions?

Red pulp: filters blood; contains RBCs, platelets, and macrophages. (bulk of spleen, rbc disposal)
White pulp: immune function; formed by lymphocytes surrounding arterioles

What is the function of the spleen's white pulp?

It contains PALS (T-cell rich), lymphoid follicles (B-cell rich), and the marginal zone (macrophages and slower innate like B cells) allowing immune responses to blood-borne antigens.

What is important about how the spleen filters antigens?

The spleen is not connected to lymphatics. It filters antigens directly from the blood, making it especially important for blood-borne pathogens.

What is the marginal zone of the spleen?

The area surrounding lymphoid follicles that contains macrophages, few T cells, and marginal zone B cells.

What is the function of marginal zone B cells?

They rapidly produce low-affinity antibodies against bacterial capsular polysaccharides, providing early protection before a full adaptive response develops.

What happens to dendritic cells after they capture antigen in the splenic marginal zone?

They migrate into T-cell areas, where they present antigen to T cells.

What are the five major principles of cytokine behavior?

• Potency: low concentrations can have strong effects

• Pleiotropy: one cytokine → different effects in different cells

• Redundancy: different cytokines → overlapping effects

• Synergy: combined cytokines amplify/reshape responses

• Cross-regulation: one cytokine can enhance or inhibit another pathway

What factors determine the effect of a cytokine?

Receptor expression, cell state, dose, and timing.

What do Type I interferons (IFN-α and IFN-β) do?

• Produced by most nucleated cells

• Induce antiviral proteins

• Inhibit viral replication

• Increase MHC I expression

• MAIN ROLE: warning system
  → Create an antiviral state in nearby cells.

What does Type II interferon (IFN-γ) do?

Produced mainly by NK cells and T cells. It activates macrophages and increases antigen presentation.

key role: adaptive immune responses against intracellular pathogens

What does Type III interferon (IFN-λ) do?

Provides antiviral protection primarily at epithelial/mucosal surfaces, especially respiratory and intestinal epithelium.

What is the key concept about interferons

They do not directly kill viruses. They change the state of host cells to resist infection and enhance immune defenses.

What is the veterinary significance of IFN-τ?

IFN-τ is a Type I interferon produced by the ruminant conceptus that signals maternal recognition of pregnancy.

What are the major functions of TNF?

TNFs regulate inflammation, cell survival, and cell death, help coordinate innate and adaptive immune responses

What are the major functions of TNF-α

Produced by macrophages, T cells, and NK cells. It:

• Pro inflammatory cytokine

• Can trigger apoptosis or necrosis

What is TNF-β (lymphotoxin-α) and what does it do

Produced by activated T and B cells. It promotes lymphoid organ development, inflammation, and immune-cell recruitment.

What can excessive TNF cause?

Septic shock and chronic inflammatory disease.

therapeutic target: anti-TNF drugs

What are the major functions of IL-1 and IL-6

Both promote fever, acute-phase responses, and endothelial activation.

What does IL-2 do?

Promotes activated T-cell proliferation and supports regulatory T-cell survival.

What does IL-12 do? (Type 1 immunity)

Activates NK cells, promotes IFN-γ production, and drives Th1 differentiation

What does IL-4 do? (Type 2 Immunity)

Promotes Th2 differentiation and B-cell responses.

What does IL-10 do? (Immune restraint)

Acts as an immune brake by limiting inflammatory cytokine production from macrophages and dendritic cells.

What do IL-23 and IL-17 do? (Type 17 axis)

IL-23: sustains Th17 cells.
IL-17: recruits neutrophils and strengthens barrier defense.

What are chemokines & function?

Chemokines are cytokines that are a family of small chemoattractant molecules; POSITIONING CELLS

recruitment of leucocytes from blood

directs their migration in tissues guiding immune cells to the site of infection

What is the difference between inflammatory and homeostatic chemokines

Inflammatory: recruit effector cells to infection/injury.
Homeostatic: organize and maintain normal tissue/lymphoid architecture.

How do chemokines cause leukocyte migration?

• Tissue/endothelial cells create a chemokine gradient

• Leukocytes with the appropriate receptor sense it

• Chemokine signaling activates integrins → firm adhesion

• Leukocyte undergoes diapedesis

• Cell follows the chemokine gradient through tissue.

What are the major cytokine functional groups to remember

IFNs: antiviral defense/macrophage activation

• TNF, IL-1, IL-6: inflammation, fever, acute-phase response (local benefit, systemic danger)

• IL-12/IFN-γ: Type 1 immunity

• IL-4/IL-13: Type 2 immunity

• IL-10/TGF-β: immune restraint, tolerance, repair

• Colony-stimulating factors: leukocyte production/survival/maturation

• Chemokines: cell positioning and recruitment

How can cytokines cause disease when dysregulated?

• Septic shock: excessive systemic TNF, IL-1, IL-6 → vasodilation, vascular leakage, hypotension, coagulation abnormalities, organ injury

• Chronic inflammation: persistent leukocyte recruitment → tissue damage

• Autoimmunity: failed regulation → persistent self-reactive lymphocyte activation

• Tumors: cytokines can suppress antitumor immunity, promote angiogenesis, and remodel tissue.

What is the key framework for understanding any cytokine

Source: What cell produced it and why?
2. Target: Which cells have the receptor?
3. Range: Autocrine, paracrine, or endocrine?
4. Outcome: Does it affect activation, differentiation, survival, or movement?
Bottom line: Cytokines change cell state; chemokines organize cell location; context determines whether the response is protective or pathological.

What do cytokines do and give examples of groups

hematopoiesis

development, activation, and suppression of immune cells

direct immune responses

Ex: interleukins, colony stimulating factors, interferons, tumor necrosis factor, chemokines

What are the major components of the innate immune system?

• Physical barriers

• Cellular components

  • Sentinel cells

  • Professional phagocytes

  • NK cells

  • gamma delta T cells

• Non-cellular components

  • Complement

  • Acute-phase proteins

  • Polyreactive antibodies

What is the first line of defense of innate immunity?

Physical and chemical barriers that prevent pathogens from entering or establishing themselves in the body

How does intact skin protect against pathogens?

• Most organisms cannot penetrate intact skin

• Wounds heal rapidly

• Sweat has an acidic pH

• Sebaceous glands produce lysozyme and fatty acids

• Dead outer skin continually desquamates, removing pathogens

What antimicrobial substances help defend epithelial barriers?

Lysozyme, phospholipase A, defensins, cathelicidins, and surfactant on alveolar surfaces. These are found in secretions such as tears, sweat, saliva, and respiratory/intestinal secretions.

How do the respiratory, GI, and urogenital tracts protect against pathogens?

• Respiratory: hair, turbinates, cilia, mucus, coughing, sneezing, mucociliary escalator

• GI: saliva, acidic pH, bile, peristalsis

• Reproductive/urinary: acidic pH and urination

What is the role of normal microflora/microbiome in innate immunity?

Normal microflora prevent pathogens from establishing on skin and mucous membranes by competing for nutrients and physical space.

What are sentinel cells and what is their primary function?

Sentinel cells are cells positioned throughout the body—especially beneath body surfaces—that recognize and respond to invading microbes or tissue damage, initiating innate immune responses.

What are the major sentinel cell types?

• Tissue-resident macrophages

• Dendritic cells

• Mast cells
  Other cells can act as sentinels, including epithelial cells, endothelial cells, fibroblasts, and keratinocytes.

What do PRRs recognize, and what are MAMPs and DAMPs?

Pattern-recognition receptors (PRRs) detect threats.

• MAMPs: microbial-associated molecular patterns

• DAMPs: damage-associated molecular patterns