Immunology Exam 1

The first vaccination was created by Edward Jenner to fight

smallpox

The first vaccination came from

the vaccinia virus (cowpox)

Commensal species

• Typically do not cause harm to the host.

• Likely become killed off from a round of antibiotics.

• Can be present in many different parts of the body.

Gram-positive bacteria example

Staphylococcus

Gram-positive bacteria

Thick cell wall containing teichioc acids

Innate Immune system

• Sets up the adaptive immune system (after breach)

• Fast response

Activates the adaptive with dendritic cells and FDC’s

• Activates inflammatory response

• Fixed (does not change or adapt to recognize new pathogens

• Uses different type of receptors

• Operates in both first and second immune response

Adaptive Immunity

• Slow response

• Variable (adaptive)

• remembers microbes

• Uses one type of receptor

• Operates during second immune response

Inflamation

• occurs when a pathogen gains entry through the surface of a wound

• causes redness, heat, pain, and swelling

• can be triggered by non-infectious factors

• results in increased vasodilation (to bring more blood and immune cells to the area) and increased vascular permeability (to let fluid and white blood cells exit the bloodstream into the tissue).

Vaccines:

Provide protective immunity against a specific pathogen, by stimulating the adaptive immune response for the body to gain memory of it.

gold standard: neutralization (surrounding the pathogen with antibodies to prevent it from causing harm to us)

Clonal selection and expansion

the process the immune system uses to find and multiply the exact B cells and T cells needed to fight a specific infection (adaptive immune response)

Lymphocytes

• include 20-50% of WBC: T-cells, B-cells, and NK cells

• all are lukocytes

• most have never been activated

• include both innate and adaptive response

Natural Killer Cells (NK cells)

• Innate Viral Fighters

• large granular lymphocytes

• full nucleus

• secrete cytokines

• help prevent viral replication + activate t-cell mediated immunity

• Kills infected host cells by apoptosis ( tells them they must die)

Neutrophil

• Best innate killing machine; first out in mass

• granulocyte

• neutral staining (lightest)

• most abundant

• stored until needed, released in mass numbers when needed

• Phagocytic (capture and kill microorganisms)

• short-lived

• Oxygen dependent mechanism of destruction: O2 turn into radicals (weapon killing pathogen)

• Oxyget independent mechanism of destruction: Defensins (poke holes into pathogen)

• accumulation of dead neutrophils →pus

Monocyte (mononuclear Phagacytes)

• precursor of macrophages, dendritic cells, or mast cell

• located in blood (steal two o’s from monocyte)

• phagocytic

Macrophage

• located in the tissue

• phagocytosis and killing of organisms

• activation of T-cells and initiation of immune responses

Dendritic cells

• recognize and present antigens (using MHC II) to T-cells in lymphnodes

• “dendritic” comes from the similar appearance (folds) of a dendrite of the nervous system

• folds allow for maximum interaction with other cells of the immune system

• Most have MHC class II and class I molecules

• Can be found in secondary lymphoid tissues

• use many PRRs (pattern recognizing receptors)

Follicular Dendritic cells

• only found in follicle of lymphnode

• B-cells will be directed to FDC in lymphnodes

• Harbor antigen for B-cell to check

Mast Cell

• tissue bound

• bind immunoglobulin E (IgE) antibodies on a surface

• innate

• get rid of parasites by the release of granules containing histamine and other active agents

• mediator→ releases histamine result of allergies

Eosinophils

• granulocyte

• redish staining (middle)

• kill antibody coated parasites through the release of granule content

• innate but work w adaptive cells

• red granules

Basophil

• granulocyte

• Darkest staining

• control immune response to parasites

• Histamine related

• innate but work w adaptive cells

• least abundant type of leukocyte

• blue granules

megakaryocyte

• make platelets

• come off erithro pre cursor

Erythrocytes

• carry lose antigen + antibody to the liver to be cleared by kupffer cells

• rumba of immune system

Naiive lymphocytes

(B+T cells) never been activated

Effector cells

• plasma cell: terminally differentiated affectpr B-cell

• cytokine producing T-cell: helper T-cell/ CD4 cell

• Cytotoxin T-cell (TC) = CD8 cell

Hematopoiesis

• the generating of cellular elements of blood

• occurs in the bone marrow

• B-lymphocytes arise and mature in bone marros

• T-lymphocytes arise in bone marrow but mature in thymus gland

common myeloid cell precursor

• made from Hematopoietic cells

• precursor of megakaryocyte-erythroid precursor cell, granuloocyte precursor cell, Monocyte, dendritic cell, and mast cell

• will eventually generate Monocytes/macrophages, dendritic cells, mast cells, neutrophils, eosinophils, basophils

Megakaryocyte-erythroid precursor cell

Precursor of Erythroblasts (make erythrocyte) and megakaryocyte (make platelets)

Granuloocyte precursor cell

precursor of basophil, eosinophil, and neutrophil

Common lymphoid cell precursor

will eventually generate B cells, T cells, NK cells, innate lymphoid cells (ILCs)

Common ILC precursor

Precursor of NK cell, ILC1, ILC2, ILC3, LTi

Common CD4 T-cell precursor

precursor of T-reg, TH17, TH2, TH1

Phagocytosis

• The process where phagocytic immune cells are specialized to capture, engulf, and kill microorganisms

• receptor recognition → pseudopodia wrap around target → target enters a phagosome → lysosomes fuse → phagolysosome → destruction

T-cell receptors

• are highly specific

• made of 2 chains

• membrane bound

Antigen

foreign substance

BCRs

• direct/ native antigen recognition

• membrane bound form of immunoglobulin

• secreted by activated B-cells

• differentiated from antibody by C-term

• Ig’s receptors (immunoglobulin’s receptors)

Helper T-cell/ CD4

release cytokines (signals) to activate other immune cells

Plasma cell

• specialized, fully differentiated B cells that factory-produce and secrete large amounts of antibodies

T-cell activation

When a T cell is activated, it undergoes clonal expansion (cell division) and differentiates into effector and memory T cells

Secondary Lymphoid tissues

• Lymph nodes: serve as the main sites where mature T and B lymphocytes encounter antigens and become activated, can swell during infection

• Spleen: filters blood, traps blood-borne pathogens, and initiates immune responses against them

• Peyer’s patches: located in the mucosa of the small intestine, trigger immune responses and stimulate the production of immunoglobulin A (IgA), which neutralizes pathogens along the mucosal lining

Pathogen associated molecular patterns (PAMPs)

• molecules on microorganisms that the innate immune system recognizes as foreign and triggers a rapid defense response

• Lipopolysaccharides (LPS/gram-negative), Peptidoglycans and Lipoteichoic Acids (gram-positive), Flagellin, Carbohydrates and Glycans (fungal)

Gram-positive

• thick peptidoglycan and taichoic acids

• memory trick: look for T

• Include:

  • Bacillus

  • Staphylococcus aureus

  • Streptococcus

  • Mycobacterium (kinda)

Gram-negative

• thin outer membrane and lipopolysacharides (LPS)

• Include:

  • E. coli

  • Pseudomonas

  • Salmonella

  • Shigella

Process of phagocytosis

1) Bacterium becomes attached to membrane envaginations called pseudopodia

2) Bacteria is ingested, forming phagosome

3) Phagosome fuses with lysosome

4) Lysosomal enzymes digest captured material

5) Digestion products are released from cell

Primary Lymphoid tissue

• Bone marrow (where B-cells mature)

• Thymus (where T-cells mature)

Intracellular pathogen in the nucleus/cytosol vs in the vesicle

• Pathogens in the nucleus/cytosol: attacked by killing infected cell

• Pathogens located in the vesicles: are attacked by the infected cell by increasing antimicrobial activity

Complement

• It helps tag pathogens and extracellular molecules for destruction

• Can destroy pathogens directly by poking holes in the outer membrane or cell wall

• ubiquitous in blood and lymph

• Involves soluble proteases called zymogens

• a molecular defense that can be used immediately

Anaphalatoxins

• C3a, C5a (recruit Neutrophils to site of infection)

• recruit phagocytes

• lead to inflammation

• chemoattractant (recruits cells to site of infection)

• C5a is more potent

Complement receptors

• CR3 and CR4 recognize iC3b

• CR2: a B-cell co-receptor, recognizes C3d

• CR1 recognizes C3b and C3bBb

type of bond exposed upon cleavage of C3

Thyoester bond

iC3

the product of C3 hydrolysis

iC3Bb

iC3Bb is the soluble C3 convertase of the alternative pathway

Pattern recognition receptor (PRR)

spot signs of infection or cell damage to trigger immune response

Variola virus

causes small pox

opportunistic pathogen

cause disease if the body’s defenses are weakened or is found in an unusual place in the body (ex.aids)

Bacteria (ex)

mycobacteria tuberculosis

• causes tuberculosis

Viruses (ex)

• HIV → AIDS

• Influenza → Flu

• Variola → small pox

Fungi

Candida albicans → Thrush, systemic candidiasis

Parasites

Trypanosoma brucei → sleeping sickness

Defensis =

antimicrobial peptide

ILC3

• secrete IL-17 (cytokine)

• innate vertion of T helper 17

• recruits neutrophils → promotes phagocytosis

• secretes antimicrobial peptides

• responds to extracellular infections, bacteria and Fungi

ILC2

• secretes IL4 and IL5

• innate version if T helper 2

• responsible for non inflammatory macrophage activation

• responds to intestinal parasites, infections

ILC1

• secrete interfering gamma

• innate version of T helper 1

• inflammatory macrophage activation

• respond to extracellular infections and bacteria

NK

• secrete interfering gamma

• Innate version of CD8

• use cell mediated cytotoxisity

• respond to intercellular infections by viruses and some bacteria

alpha-2-macroglobulin

• A protease inhibitor

• cuts its “bait” by enclosing the protease and creating an “eat me signal” for phagocytes

where are acute phase proteins made

Liver

where are M Cells located

in the lining of Peyer's patches

Steps of inflammation

Inflammatory cytokines activate endothelium → vasodilation (widening of blood cells) + increased vascular permeability (rushing blood to injured area) + new adhesion molecules → leukocytes can leave blood and enter tissue.

Endema

swelling from fluid/cells/molecules entering tissue

Barrier breach→

Macrophage recognize PAMP with PRRv→ Macrophage realease cytokines/chemokines → endothelial activation (activation of inflammation) → vasolation/permeability/ adhesion (inflammation) → neutrophil recruitment → destruction of pathogen

Opsonin

• a host molecule that tags/coats a target to make it easier for a phagocite to recognize and ingest

• C3b and C4b act as a opsonin (recognized by CR1)

• C3b and C4b attach covalently to microbial surfaces by thioester bond after nuophilic attack

• Certain antibodies can act as opsins

Erythroid precursor

will generate Erythrocytes and megakaryocytes → platelets

Naivve B/T cells

• not yet activated

• little cytoplasm (not yet producing large quantities of effector molecules)

Kupffer cells

Macrophage in liver

Microglia

Macrophage in brain

Tfh (follicular helper cells)

• innate version of Tfh (follicular helper cells)

• Activate B cells

• suppress immune system

MHC (major histocompatibility complex)

TCR recognizes the combination of MHC amino acids + presented peptide

amino acids

MHC I

• Used by essentially all nucleated cells

• Presents intracellular peptides

• Virally infected cells can present to effector CD8 T cells

MHC II

• Restricted to professional antigen-presenting cells: dendritic cells, macrophages, and B cells.

Extravasation

• movement of cells of of the blood across endothelium to tissue or lymphoid tissue

• sequence: rolling → adhesion/tight binding → diapedesis → chemotactic migration

Afferent

Arrive

Efferent

Exit

Spleen → red puld

red cell handling

Spleen → white pulp

organized secondary lymphoid tissue for blood born antigen / pathogen

MALT

• mucosal associated lymphoid tissue (mucosal surfaces)

• GALT = gut associated lymphoid tissue ( contains IgA = immunoglobuline A

• BALT = bronchus associated lymphoid tissue

• Peyer’s Patches = organized GALT with B/ T cell regions

  • continuously samples external body and supports antibody mediated neutralization

Neutralization

Antibody binds / covers pathogen so it cannot cause harm

Opsonization

Antibody binds to pathogen and is recognized by an Fc receptor leading to phagocytosis

Complement activation

certain antibodies initiate complement and lead to opsonization

Primary vs secondary adaptive immune response

• Primary = creates memory

• Secondary = acts faster + stronger

• “student surpasses the master”

TCR

Need MHC + peptide;

Draining lymphnode

• lymph node receiving material from an infected site

• a node where the adaptive response / B- and T-cell activation is occurring.

Secondary Lymphoid

• Lymph nodes, spleen white pulp, organized MALT such as Peyer's patches

• antigen meet B/T cells

Defensin Production

• epithelial cells + neutrophils

• poke holes

Acute Phase Response

• Macrophage recognizes PAMP with PRR and produces cytokines → IL-6 will travel to liver

• “IL-6 binding to hepatocytes leads to the production of Acute Phase Proteins (CRP + MBL) → more complement

• Hepatocytes = Liver cells

• CRP → classical complement pathway (complement receptor protein)

• MBL → Lectin complement pathway ( Manose binding lectin)

DAMP’s

• damage associated molecular patterns

• signals from damaged/dead host tissue that promote clearance and wound healing even without infection.

Recognition of a PAMP by a signaling PRR drives

six inflammatory cytokines: TNF-alpha, IL-1, IL-6, CXCL8, CCL2, IL-12

TFN-alpha

• Endothelial activation

• cting on nearby endothelium = paracrine

IL-1-beta

• Endothelial activation(Identical to TNF)

• induces fever

• acting on nearby endothelium = paracrine

IL-6

• acts on Liver/ hepatocytes to make acute phase proteins

• “I Love 6 pack abs” (abs=core=liver)

• traveling to liver = endocrine

TNF-alpha, IL-1, IL-6 are

pyrogens: act on hypothalamus/ body systems to increase temp and promote bone marrow output

CXCL8

• chemokines that recruite neutrophils

• Neutrophils 8 bacteria