Immuno Exam 1

Immunity

hosts collective reactive to a foreign antigen

• all mechanisms that protect against disease

Immune system

organized network of cells and molecules responsible for immunity

Immune response

• specific, coordinated reaction of the immune system against a foreign substance

  • can be innate or adaptive

Antigen

any substance recognized by the immune system

• triggers a response

Innate/natural

• rapid, pre-existing defenses present before any exposure

• acts within minutes to hours

  • no memory

Adaptive (acquired)

• delayed, antigen specific response

• takes days to weeks to develop

  • builds memory for faster future responses

How can an antigen not be an immunogen?

if it lacks size, complexity, or foreign status required to independently trigger an active immune response

Anatomical barriers of the immune system?

• Skin (SS epithelium, keratin blocks entry, fatty acids = low pH)

• Mucous membrane (traps pathogens and cilia sweeps)

Secretory barries

• saliva and tears (lysozyme and lactoferrin)

• normal flora (normal residents will fight invaders)

Physiological barriers

• temperature (pyrexia)

• low pH (gastric acid, vaginal and urinary)

Innate system recognizes danger how?

• PAMPS

• DAPMs (alarmins)

• PRRs

PAMP’s

• pathogen associated molecular patterns

• conserved microbial molecules

• absent in healthy host cells

Example of PAMP’s

• LPS, peptidoglycan, flagellin, dsRNA

DAPMs

• alarmins

• damage-associated molecular patterns

  • released from stressed, dying, or damanged host cells

Example of DAPM’s

• HMGB1, uric acid, heat shock, proteins

PRR’s

• host cell receptors that detect both PAMP’s and DAMP’s, triggers innate defense cascades

PRR example

• toll like receptor

• NOD like receptor

• C-type lectin

TLR4 (PRRs)

• cell surface

• LPS

• bacteria and viruses

TLR5 (PRR)

• cell surface

• flagellin

• bacteria

TLR9 (PRR)

• intracellular

• CpG DNA, dsDNA

• viruses, bacteria, protozoa

What cells and molecules make up the innate immune system?

• sentinel cells

• inflammatory cytokines

Innate Sentinel Cells

• armed with PRR’s

• just below body surfaces

  • macrophages

  • dendritic cells

  • neutrophils

  • mast cells

Innate pro-inflammatory cytokines

• IL-1

• IL-6

• TNF-a

• IL-8

IL-1

• activates leukocytes and endothelium

• fever

• acute phase response

IL-6

• activates leukocytes

  • drives acute phase protein synthesis (fibrinogen, CRP) in liver

TNF-a

• activates leukocytes and endothelium

• high levels = septic shock

IL-8

• cxcl8

• chemokine

• recruits neutrophils to site of infection

Is previous exposure necessary for an effective innate immunity?

no

• effectiveness is not improved with repeated exposure

What is primary ciliary dyskinesia (PCD)?

• autosomal recessive

• cilia structure is abnormal and mucociliary escalator is non-functional

• bacteria cn accumulate

Describe the innate TRL-mediated response to bacterial lipopolysaccharide (LPS)?

• endotoxins from gram (-) stimulate macrophages to release cytokines

• endotoxins active pro-inflammatory enzymes

• sepsis syndrome

  • overall, overwhelm innate immune response and disease is the result

Humoral Adaptive Response

• targets extracellular invaders

• uses B cells → plasma cells → antibodies (immunoglobulins

Cell-Mediated Adaptive Response

• targets intracellular invaders (viruses, intracellular bacteria)

• CD8+ directly kill infected cells, CD4+ T helpers orchestrate that response

B lymphocytes

• mature in bone marrow

• recognize extracellular antigens via BCR and memory B cells

• produce IgM (primary) → IgG (secondary, after class switching)

T lymphocytes

• CD4+

• CD8+

• CD17+

• Treg

CD4+ T Helper (TH)

• Orchestrates the response

• Helps B cells make antibodies and activates CD8+ T cells

• critical for effective immunity

CD8+ CTL (cytotoxic)

• direct killing of virus infected and tumor cells

• recognizes MHC Class 1+ antigen

• Perforin/granzyme mechanism

CD17+ (Th17)

• pro-inflammatory at mucosal surfaces

• produces IL-17

• critical for fungal and bacterial defense at barriers

Treg (Regulatory T)

• stop inflammation when infection is cleared

• prevents autoimmunity

• produces IL-10 and TGF-B

Is previous exposure necessary for an effective adaptive response?

yes

• because your cells need to develop a response

Primary response

• lag period (7-14 days)

• predominant antibody (IgM: first responder)

• lower antibody titer

• memory B and T cells generated

Secondary response

• faster (1-3 days)

• IgG is predominant (higher affinity/longer lasting) - isotope switching

• 10-100x higher igG concentration

• more specific clones produced

Memory in cell mediated immunity (Graft Rejection)

• body identifies foreign MHC molecules as non-self

• T cells mount cytotoxic + inflammatory attack

• 1st graph: primary (rejection occurs over 7-14 days)

• 2nd graph: second (anamnestic response, rejected acceleration (3-5 days), demonstrates cell mediated immunity

Key things about adaptive immunity:

• antigen specific

• immunological memory

• improves over time

• self vs. non self

• delayed onset

• augments innate

What are the professional antigen presenting cells?

Dendritic cells

• capture and present antigens

What is an “epitope”?

specific tiny spot on foreign object that the immune system recognizes and attaches to

What is a pluripotent stem cell?

• can divide without limit and turn into any cell type in the body

What is the function of a primary lymphoid organ? What happens there?

• lymphocyte generation and maturation

  • antigen indepdent

What are the primary lymphoid organs?

• thymus, bursa of fabricius, bone marrow, peyers patches

Mammals do not have a bursa, what are their bursal equivalents?

bone marrow

What are the primary lymphoid organs of birds?

Burse Fabricius

What are the primary lymphoid organs of ruminants?

Peyers Patches

Why is dysfunction of the primary lymphoid organs important?

• if lost, it results in severe, early lifelong immunodeficiency

Thymus

• primary

• cortex contains dense T cells that undergo rapid proliferation

• medulla contains mature T cells + Hassalls corpuscles

Where is the only site of T development?

• thymus

  • trains cells to recognize MHC without attacking self (education)

Thymic Education: Positive selection

• cells w moderate affinity for self-MHC survive

Thymic Education: Negative selection

• self-reactive cells (too-high affinity) are delete

Thymic Involvement

• begins at puberty

• tissue is replaced by fat

  • T cell output declines w age

Bursa Fabricius

• B cell maturation and antibody repertoire generation

• involutes with maturity

Why are the chickens affected with infectious bursal disease are susceptible to other infections?

any bursal damaged in early life causes lasting B cell deficits

• causes increased susceptibility to coccidiosis, Marek’s disease, and colibacillosis

What is the function of a secondary lymphoid organ? What happens there?

mature lymphocytes actually meet the antigen

What are the secondary lymphoid organs?

• lymph nodes

• spleen

• MALT/GALT

MALT/GALT

• mucosal surfaces (gut, resp. tract, mammary gland)

  • constant antigen exposure

What are the functions of a lymph node?

• antibody producing B cells develop (cortex)

• T cell zone, allows lymphocytes to enter from blood (paracortex)

• Plasma cells and lymphatics (medulla)

• Afferent/efferent flow (lymph enters via afferent and exits one efferent)

GALT (gut)

• M cells ontop of peyer’s patchs

• sample luminal antigens and passes it to underlying lymphoid follicles

• output: plasma cells secreting IgA (transported across epithelium to protect mucosal surface directly)

Spleen: 3 functional zones

• Red pulp

• White pulp

• Marginal Zone

Spleen functional zones: Red pulp

• vascular sinuses that store and filter RBC

Spleen functional zones: white pulp

• PALS or periarteriolar sheaths (T-cell zone around arterioles) and follicles (B-cell zone)

Spleen functional zones: Marginal zones

macrophages and dendritic cells that capture blood borne antigen first

What are the four main functions of the spleen? Are they all immunological?

• Host immune response (antigen processing and present)

• filtration of unwanted elements from blood via phagocytosis

• hematopoiesis (mainly in fetus)

• reverse blood storage

How do lymphocytes get from primary to secondary lymphoid organs?

bloodstream

Risk of splenctomy

• loss of splenic filtration

• risk for tick borne pathogens (cannot clear intraerythrocytic parasites)