Intro to innate and adaptive immunity

Myeloid

innate responses (erythroid, granulocytes, agranulocytes)

Lymphoid

generally adaptive responses (lymphocytes, natural killer (NK) cells)

Erythroid

RBCs, anucleate when mature, platelets=magekaryocytes

granulocytes

neutrophils, eosinophils, basophils

neutrophils

phagocytic, most abundant (ex: PMNs)

Eosinophils

parasitic worms and allergies

basophils

inflammatory, allergies

monocyte/macrophage

phagocytic, antigen presenting cells (APC)

Dendritic cells

phagocytic, APC

Mast cells

inflammatory, allergies

lymphocytes

B,T- antigen specific

natural killer (NK) cells

NON antigen specific, recognize altered-host cells

most and least abundant WBC types

most: neutrophil (40-75%)

least: basophil: <1%

Neutrophils (PMNs)

typically first to arrive at infection, associated with bacterial infections

Basophils and eosinophils

-release pro-inflammatory factors

-relatively low % in blood

-associated with allergies (eosinophils=worm infections)

dumbell shape= eosinophil

purple-black granules= basophil

Monocytes

-phagocytic

-LARGEST wbc

-in tissue develop into macrophages

-bridge adaptove and innate resposnes

kidney shape= monocyte

Lymphocyte

-T or B lymphocyte

-adaptive responses that are antigen specific

left= resting lymphocyte (big circle inside)

right= reactive lymphocytes

where do blood cells originate

bone marrow, specifically hematopoietic stem cells expressing CD34 protein

where do RBCs and some WBCs originate from

myeloid lineage

where do lymphocytes originate from

lymphoid lineage

myeloid cells

granulocytes and agranulocytes, for innate defenses

Lymphoid cells

-the adaptive defense, forms lymphocytes and includes B and T lymphocytes

-NK cells are from here, but not part of adaptive responses

Innate immunity

-born with

-fast acting

-barriers, cells, and seurm proteins

Acquired (adaptive) immunity

-improves with exposure

-primarily mediated by lymphocytes (T and B cells)

Cells of innate immunity

NK cells, macrophages, dendritic cells, granulocytes

Cells of acquired immunity

T and B lymphocytes

Innate immunity soluble mediators

cytokines, chemokines, defensins, pentraxins, complement

Acquired immunity soluble products

Cytokines, chemokines, antibodies

Innate immunity: first lines of defense (6)

-saliva (antibacterial enzymes)

-tears (antibacterial enzymes)

-skin (prevents injury)

-stomach acid (low pH kills harmful microbes)

-mucus lining (traps dirt and microbes)

-’good’ gut bacteria out compete the bad

phagocytes

destroy infected/damaged cells via phagocytosis

NK cells

Lytic (related to destruction of cell membrane)

cytokines and chemokines

pro-inflammatory and chemotactic (moves cells)

Lysozyme

antimicrobial molecules

Complement cascade

Cell lysis, inflammation, and opsonization

Inflammation

isolate, recognize, and destroy microbes

4 Phagocytosis steps

1. chemotaxis

2. recognition

3. ingestion

4. digestion

General phagocytosis process

neutrophils and monocytes/macrophages engulf microbes and cell debris of injured tissues

Pus formation

PMNs die after digesting debris and release a liquid to liquify bacteria, this forms pus

Complement cascade

-involves 30 different proteins

-cascade of events results in cell lysis, opsonization, and/or inflammation

-mostly made by liver cells

-MOST effective against bacterial infections

3 complement casdade pathways

-classical

-MB-lectin pathway

-alternative pathway

Classical pathway

-antigen=antobody complexes

-C1q, C1, C1s, C4, C2

MB-lectin pathway

-mannose-binding lectin binds mannose on pathogen surfaces

-MBL, MASP-1, MASP-2, C4, C2

Alternative pathway

-pathogen surfaces

-C3, factor B, factor D

C’ activation responses

-cell lysis (MAC, membrane attack complex)

-opsonization of Ag (tagged substance removed by C3b)

-mediated inflammation (products bind to mast cells, basophils and neutrophils, releasing histamine), involves C3a and C5a

MAC (membrane attack complex) of complement cascade

Interferons (3 types)

IFN-alpha, IFN-beta, IFN-gamma

IFN-alpha and IFN-beta

-have direct anti-viral effects

-made by mostly virally infected cells

IFN-gamma

-made by immune cells (T and NK cells)

-key in immune system activation

-NK cells=innate defense, kill altered self cells

IFN-alpha,beta (with IFN attachment to special receptor)

Lysozyme

-made by cells of the mucous membrane (tears, saliva, mom’s milk)

-hydrolyzes the beta-1,4 linkage of bacterial peptidoglycan

Arrow shows the beta-1,4 linkage that lysozymes hydrolyze

Cardinal signs of inflammation

-heat (calor)

-redness (rubor)

-pain (dolar)

-loss of function (functio laesa)

Histamine

along with other chemicals stimulates increased blood flow

3 pro-inflammatory cytokines

-Interleukin 1 (IL-1)

-interleukin 6 (IL-6)

-tumor necrosis factor alpha (TNF-alpha)

Heat

-increased blood flow to area

-localized increase in pressure

-inc chem rxns, inc cell activity

Redness

-increased blood flow to area

-more RBC and WBC to area

Swelling

-smooth muscle dilation

-fluid accumulation

Pain

-release of chemicals to stimulate nerves

--bradykinin and prostaglandin E2 (PGE2)

Loss of function

combination of factor

Inflamed periodontitis

inflammation along with T cells (cytokines) and antibodies cause tissue damage

immune response barriers

skin and mucous membranes

immune response cells

phagocytic and NK cells

immune response chemicals

complement cascade and interferons (IFNs), lysozymes, inflammatory cytokines

adaptive defenses are primarily from

Action of B and T lymphocytes

C3 Convertase of complement cascade

-C3a and C5a—>inflammation

-C3b—>binds to phagocytes—>pathogen opsonization

-C3B—>terminal complement components(C5-C9)—>lysis of certain pathogens and cells

1st line of host defense

(non-specific) skin, mucous membranes, chemicals

2nd line of host defense

(nonspecific) phagocytosis, complement, interferon, inflammation, fever

3rd line of host defense

(specific) lymphocytes, antibodies

2 types of major immune organs

primary and secondary lymphoid organs

primary lymphoid organs

-central

-site of immune cell development

-bone marrow and thymus

secondary lymphoid organs

-peripheral

-where immune response is generated (rec Ag)

-lymph node, spleen, blood, and MALT

-germinal center=site in LN of activated B cells

when are self-reactive cells destroyed

should be destroyed early in development of B and T cells, those NOT silenced undergo antigenic tolerance (are silenced)

B cells mature in:

mature in the bone marrow

T cells mature in:

mature in bone marrow and Thymus

B and T cell receptors

-antigen receptors determine specificity

-B cell receptor: BCR-Ab, Ig on B cell

-T cell receptor: TCR on T cells

Fab region=variable region= where antigen binds on B cell

Variable region = where antigen binds on T cells

antigens can be:

protein, carbohydrate, lipid, or nucleic acid

antigen can be found from:

bacteria, virus, protozoan, worm, and kidney (extracellular or intracellular microbes)

B cells recognize:

Soluble Ag (antigen) in conformation configuration

B cell Ag can be:

-protein or carb (most common)

-nucleic acid or lipid (rare)

Denaturation often prevents Ab binding

T cells recognize:

processed Ag that’s presented with MHC (major justocompatibility complex)

MHC/HLA proteins

-proteins on surface of our cells

-Class I MHC=on all nucleated cells

Class II MHC= on professional Antigen presenting cells (ex: B cells)

T cells are usually:

protein or peptides

T lymphocyte epitope

Antigen presenting cells (APCs)

present protein Ags to T cells

Professional APCs

Macrophages, dendritic cells (DCs), and B cells

Target cells

present antigenic peptides via MHC class I molecules

Target cell (an infected cell)

Antigen-presenting cell, a macrophage

Activated immune cells produce:

effector cells and memory cells

memory cells

-quicker and better response (to rec ag)

-secondary immune response=a few days

-subsequent exposure to same Ag=1-3day response, better

-rationale for vaccine

Vaccination (2 types)

-passive= immune system products from another (mom’s milks, gamma globulin)

-active= stimulate individual’s immune system to produce memory cells

the effector cells:

Th1 and Th2

adaptive/acquired immune response 4 properties

1. self versus non-self recognition

2. specificity

3. heterogeneity

4. memory