MICR 3230 Midterm Exam

What is immunity?

The state of protection against foreign pathogens or substances (antigens)

How do you generate immunity without disease?

Immunization

What does immunization do?

Prepares the immune system for eradication of the antigen

What is herd immunity?

Vaccination/protection of a critical mass of people

What is humoral immunity?

Combats pathogens via antibodies

What are antibodies produced by?

B cells

2 types of humoral immunity:

Passive & active

What is cell-mediated immunity mediated by?

T lymphocytes

How does cell-mediated immunity work?

Eradicates pathogens, clear infected self-cells, aid other cells in immunity

Humoral & cell-mediated immunity rely on:

Surface receptors of B and T cells

Receptors are randomly generated by:

Gene segment rearrangements in the cells

B cells that encounter antigen produce:

Specific antibodies

T cells:

Bind antigens/specific peptides presented by APCs

General gist of humoral immunity:

BCR binds antigen

Antigen internalized

B cell produces antibodies

General gist of cell-mediated:

TCR binds antigen

T cell produces cytokines

OR

TCR binds antigen

Antigen internalized

Infected cells recognized by APCs & lysed

4 major categories of pathogens:

Viruses

Bacteria

Fungi

Parasites

What is pathogen recognition?

An interaction b/w foreign organism & recognition molecule expressed by host

Ligands include:

Whole pathogens

Antigenic fragments

Products secreted by foreign organisms

The immune response is:

An extra-/intracellular cascade of events leading to the labeling & destruction of pathogen after ligand binding

Cells that recognize & kill/engulf pathogen labelled:

CELLULAR immunity

Soluble proteins for labeling & destruction of invaders labelled:

HUMORAL immunity

Immune responses rely on:

Recognition molecules

Recognition molecules are:

Encoded in DNA - always expressed - PRRs

PRRs bind to PAMPs

Randomly generated

Explain clonal selection:

Individual B and T cells have specificity for single antigen

Each has many copies of a receptor that only binds to 1 antigen

When B or T cell reacts w antigen it's SELECTED & ACTIVATED

Activation --> proliferation --> large # of clones

Each clone responds to original pathogen

Cells not activated are deleted

Tolerance ensures:

That the immune system avoids destroying host tissue from anti-self antibodies

2 systems that respond to pathogens:

Innate

Adaptive

The innate system:

First line of defence

Fast but NOT specific

Uses inherited recognition molecules & phagocytic cells

The adaptive system:

Humoral & cell-mediated

Slow (5-6 days)

Uses randomly generated antigen receptors

Highly specific

How do the innate & adaptive systems work together?

The innate gives out signal molecules (cytokines & chemokines) that direct adaptive response

Primary response (memory):

First exposure to the antigen

Memory lymphocytes left behind after the antigen is cleared

Secondary response (memory):

Second exposure stimulates the memory lymphocytes

Faster, more significant, better response

The 2 dysfunctions of immunity are:

Overly active/misdirected

Immunodeficiency (primary or secondary)

What is the microbiome?

Commensal organisms that live on & in us causing no harm

Pushes to homeostasis

An imbalance/dysbiosis leads to inflammation

Hematopoietic stem cells have the ability to:

Differentiate into many types of blood cells

What is hematopoiesis?

Highly regulated process by which HSCs differentiate into mature blood cells

What are the primary lymphoid organs?

Bone marrow & thymus

Where immune cells develop from immature precursors

What are secondary lymphoid organs?

Spleen, lymph nodes, gut & mucosal tissue

Where mature antigen-specific lymphocytes first encounter antigen & begin the immune process

Hematopoiesis occurs in the:

Bone marrow

HSCs are constantly:

Renewed & directed to differentiate into 2 major types of PROGENITOR CELLS

What are the 2 types of progenitor cells?

Common myeloid progenitor cells - give rise to RBCs & myeloid cells (granulocytes, monocytes, macrophages, DCs); part of innate immune system

Common lymphoid progenitor cells - give rise to WBCs, B & T lymphocytes, innate lymphoid cells, NKs; part of innate & adaptive immune systems

Human blood cells' lifespan:

RBCs - 120 days

Platelets - 5-10 days

Monocytes - days to months

Basophils - hours to days

Lymphocytes - days to years

4 main types of cells develop from common myeloid progenitors:

RBCs

Monocytes

Granulocytes (neutrophils, basophils, eosinophils)

Megakaryocytes

What do all granulocyte subtypes have?

Large nucleus & granules containing cytotoxic enzymes & antimicrobial peptides

Granulocytes - neutrophils:

Multilobed nucleus

Granules contain:

Proteases - tissue remodelling, protein degradation

Antimicrobial proteins - direct harm to pathogen

Protease inhibitors - regulation of proteases

Histamine - vasodilation, inflammation

Granulocytes - eosinophils:

Granules contain:

Cationic proteins - induces formation of ROS, vasodilation, basophil degradation

Ribonucleases - antiviral activity

Cytokines

Chemokines - attract leukocytes

Granulocytes - basophils/mast cells:

Granules contain:

Cytokines

Lipid mediators

Histamine

Monocytes function is:

Migrate into tissue & differentiate into macrophages

Repair/remodel, destroy pathogens, present antigens

Differentiate into DCs - ingestors

When professional APCs encounter a pathogen (3 steps):

1. Secrete proteins that attract & activate other immune cells

2. Internalize pathogens via phagocytosis, digest pathogenic proteins into peptides, present peptide antigens on membrane surfaces via MHC II molecules

3. Upregulate costimulatory molecules required for optimal activation of T helper cells

Macrophages & neutrophils are specialized for:

Phagocytosis

Macrophages present antigens to ____ via ____:

T cells; MHC molecules

Immature DCs ___ antigen then ___ & ___:

Capture; mature & migrate to present to T cells

The most potent APCs are for:

Activation of naive T cells

The 3 main types of cells that develop from common lymphoid progenitors:

B lymphocytes

T lymphocytes

NK cells

Different lymphocytes carry different:

Sets of CD molecules

What is CD4?

Binds to MHC II

Signal transduction

T helper

What is CD8?

Binds to MHC I

Signal transduction

T-cytotoxic

Lymphocyte maturation:

Naive - newly formed B & T

Effector - contact w/ antigen

Memory - contact w/ antigen, effector cloned

B cells express what receptor?

BCR

T cells express what receptor?

TCR

During embryogenesis & the fetal period blood cell formation shifts:

Side to side

Hematopoiesis begins in the:

Yolk sac

Fetal HSCs arise near the:

Kidney

Mature HSCs capable of populating the hematopoietic system can be isolated from:

Yolk sac

Placenta

Fetal liver

Postnatally HSCs populate the:

Bone marrow

Stromal cells facilitate:

HSC proliferation

Direct migration

Stimulate differentiation

T cells develop initially in the ___ & then migrate to ___ to mature:

Bone marrow; thymus

What directs stepwise changes in thymocytes?

Microenvironment of the thymic cortex & medulla

TCR affinity of binding w/ MHC peptides drive:

Positive & negative selection

Positive selection = self/non-self recognition w/ intermediate recognition of TCR to MHC

Negative selection = self/non-self recognition w/ high affinity binding of TCR to MHC

If thymocytes bind to self MHC too strongly they:

Are negatively selected & die

What are the lymph nodes, spleen & MALT connected by?

Blood & lymphatic systems

What are the most highly organized parts of the secondary lymphoid organs?

Lymph nodes & spleen

B cells act in the:

Cortex

T cells act in the:

Paracortex

Macrophages & DCs act in the:

Innermost lymph node medulla

Antigen enters via:

Afferent vessel

Naive lymphocytes enter by:

HEV

Lymphocytes exit via:

Efferent vessel

Lymphocyte cells actively migrate towards:

Each other during activation events

Lymphoid fibroblastic reticular conduit guides:

T cells & APCs toward activation interactions

Differentiation takes place in:

Follicles

B cells - clonal expression - germinal centres

CD4+ T helper - helper T cells

CD8+ T cells - killer T cells

The spleen is the:

First line of defence against bloodborne pathogens

RBCs compartmentalized into:

Red pulp

WBCs segregated in:

White pulp

Bordering white pulp is a:

Specialized region of macrophages & B cells = MARGINAL ZONE

What is the mucosa associated lymphoid tissue?

Layer of defence against infection at mucosal & epithelial layers

What is the function of the mucosa associated lymphoid tissue?

Organizes responses to antigens that enter mucosal tissues

Includes gut associated lymphoid tissues

If the antigen breaks through the layer - immune response

If an anatomical barrier is breached:

Innate RCs recognize the threat - PAMPs

DAMPs recognize:

Aging, dead, damaged self-structures

PRRs recognize:

PAMPs & DAMPs

Target for clearance

Physical & chemical anatomical barriers:

Epithelial layers of skin

Mucosal/glandular tissue

Acidic pH

Antimicrobial proteins & peptides

Epithelial barriers:

Prevent pathogen entry into body

Skin, mucosal membrane, acidic pH, enzymes & binding proteins, antimicrobial proteins & peptides

What are the PAMP ligands?

TLRs

CLR

RLR

NLRs

What recognize PAMP ligands?

Families of PRRs

When signalling pathways are activated they contribute to:

Innate/inflammatory responses

Toll-like receptors recognize:

Many types of pathogen molecules

TLR exteriors rich with:

Leucine-rich repeats

Associated w/ ligand binding of PAMPs & DAMPs

TIR domain with:

Toll/IL 1 Rc

What activates the TLR signal cascade?

Ligand (PAMP/DAMP) induced TLR dimerization

Where are TLRs located?

In the plasma membranes of endosomes & lysosomes

After PAMP binding, different TLRs recruit different adaptor proteins to:

The Toll/IL-1R domain

Different adaptor proteins lead to different events