Lecture 1 - Intro to Immune System

Study of host's reactions to foreign substances termed "antigens":

Foreign substances that induce a host response

- pollen proteins
- components of bacterial pathogens

The condition of being resistant to infection

active and passive

when you get the flu

when you receive an antibody specific to an infectious agent

Hepatitis B Immunoglobulin (HBIG)

People inhaled powder from smallpox scabs to prevent smallpox

Developed smallpox vaccine from cowpox material?

several vaccines through attenuation

pathogens made less virulent through heat, aging, or chemical treatment

- innate/natural immunity
- adaptive/ acquired immunity

non-specific responses

specific response

- skin
- mucous membrans & secretions
- normal flora

- innate immune cells
- inflammation
- complement
- antimicrobial substances

Specialized lymphocytes
- B cells: produce antibodies
- T cells
- Helper T cells
- Killer T cells

• Also known as natural immunity
• Ability to resist infection through normally present body
functions
• Nonspecific: responses are the same for all pathogens
or foreign substances
• Prior exposure not required
• Effect is immediate
• Memory not generated

natural immunity

the ability to resist infection through normally present body fxns

Innate immunity

responses are the same for all pathogens or foreign substances

innate immunity

Innate immunity

Innate immunity

• Characterized by specificity for each antigen (e.g., individual pathogens)
• Memory is generated
• The immune system “remembers” a prior exposure to an antigen and mounts an increased response upon repeated exposure
• Memory and specificity lead to a stronger immune response upon repeated exposures
• Has two branches: CMI and HMI

adaptive immunity

white blood cells (WBC)

in the peripheral blood and lymphoid tissues

innate and adaptive immunity

Granulocytes
Monocytes/Macrophages
Mast cells
Dendritic cells

Neutrophils
Eosinophils
Basophils

Hematopoietic stem cell (HSC)

Bone marrow - through hematopoiesis

Common myeloid progenitors (CMP)
Common lymphoid progenitors (CLP)

WBCs that perform phagocytosis

lymphocytes

50% - 70%

phagocytosis and destruction of foreign particles

multi-lobed nucleus and neutral staining granules in cytoplasm

1 - 4%

• Phagocytosis (less efficient than neutrophils)
• Neutralization of products released in allergic reactions (e.g., histamine)
• Killing of parasites (e.g., helminths)
• Release of cytokines

Contain a bilobed or ellipsoidal nucleus and red-orange cytoplasmic granules

less than 1% of circulating WBCs

Release histamine and other granular contents, which induce and maintain allergic reactions

Contain a bilobed nucleus and deep blue-purple cytoplasmic granules

Basophils

2 - 10% of WBC's

up to 30h then migrate to tissues to become tissue-resident macrophages

monocytes that have migrated to the tissues

Large cells with a horseshoe-shaped nucleus, dull grayish blue cytoplasm, and fine granules

Innate AND adaptive

• Phagocytosis and microbial killing
• Anti-tumor cell activity
• Intracellular parasite eradication
• Secretion of cell mediators

• Process and present antigens to T cells
• Produce cytokines that regulate immune responses

• Resemble basophils but come from a different lineage
• Present in tissues (e.g., skin, connective tissue)
• Induce and maintain allergic reactions

• Have long membranous extensions that resemble nerve cell dendrites
• Roles in both innate and adaptive immunity
• Most potent phagocytic cell
• Most effective antigen-presenting cell (APC)

Lymphocytes

20-40%

• B cells
• T cells
• Natural killer (NK) cells

Small cells with a large, round nucleus, and sparse, light blue cytoplasm

CLP

B cells --> Plasma cells --> secrete antibodies

Surface Ig
CD19
CD20
CD21
MHC Class II

B cells

Plasma cells

Thymus

CD3+

- Helper T cells (Th; CD4+)
- Regulatory T cells (Treg; CD4+)
- Cytotoxic T cells (Tc; CD8+)

produce cytokines that stimulate B cells in antibody production - and assist other T cells in cell-mediated immunity

they inhibit immune responses

they destroy tumor cells and virus-infected cells

they have important roles in innate imunity and tissue remodeling

Natural killer (NK) cell

They are large cells with kidney-shaped nuclei and granular cytoplasm
aka large granular lymphocyte (LGL)

CD16
CD56

10-15%

- Kill virus-infected cells and turmor cells without previous exposure
- destroy antibody-coated target cells (Ab-dependent cell cytotoxicity or ADCC)

Bone marrow
Thymus

- a primacy lymphoid organ
- large tissue that fill the cor of all long flat bones
- main source of HSC's
- location of B cell maturation and T cell development

- they develop into:
erythrocytes
granulocytes
monocytes
platelets
lymphocytes

- a small flat, bilobed organ found in the thorax
- location of T cell maturation

they receive mature lymphocytes from primary lymph organs
function as sites for contact with foreign antigens

Spleen
lymph nodes
mucosal-associated lymphoid tissue (MALT)
cutaneous-associated lymphoid tissue (CALT)

- largest secondary organ
- located in the upper left quadrant of abdomen, just below diaphragm
- contains red and white pulp

rich in macrophages
destroys old RBCs

- 20% of the total weight of the spleen
- contains lymph tissue arranged around arterioles in a paerarteriolar sheath containing T cells
- B cells are in follicles attached to the sheath

- secondary lymphoid organ
- located along lymphatic ducts, especially near joints and where arms and legs join the body
- they collect lymph fluid from adjacent tissues

afferent lymphatic vessels

paracortex

- mucosa-associated lymphoid tissue (MALT)
- secondary lymphoid tissue
- found on the mucosal surfaces of the gastrointestinal, respiratory, and urogenital tracts
- main port of entry for foreign antigens
- numerous macs and lymphs present

tonsils
appendix
Peyers patches

- cutaneous-associated lymphoid tissue
- T cells, monocytes, macs, and dendritic cells found the SKIN

- lines or layers of defense that act immediately when a host is attached by a pathogen
- nonspecific
- Two types: external and internal defense systems

- type of innate immune system
- anatomical barriers to keep microorganisms from entering the body

1. skin
2. mucous membranes
3. respiratory membranes
4. respiratory tract
5. digestive tract
6. genitourinary tract
7. microbiota (normal flora)

physical barrier to pathogen entry
secretions discourage microorganism growth (sweat)

Epidermis - tightly packed epithelial cells coated in keratin (keratinocytes)
Dermis - connective tissue with blood vessels, hair follicles, sebaceous glands, and WBCs

- lactic acid and fatty acids that maintain the sin at a pH of ~5.6
- proteins with antibacterial effects (ex. psoriasin)

- they line the respiratory, digestive, and genitourinary tracts
- serve as a physical barrier to pathogen entry
- mucous secretions contain surfectants that block bacteria adhering to epithelial cells

- contain cilia in nasopharyngeal passages that clear deposited material
- coughing and sneezing remove pathogens

- stomachs hydrochloric acid keeps the pH as low as 1, prohibiting microorganism growth
- lysozyme in tears and saliva attacks cell walls of gram-POSITIVE bacteria

It flushes out pathogens
contains lactic acid that keeps the vagina at a pH ~5

helps to keep pathogens from establishing themselves in the body

It is compose of cells and soluble factors that NONSPECIFICALLY defend against foreign invaders

- pattern-recognition receptors (PRRs)
- acute-phase reactants
- inflammation
- phagocytic cells
- natural killers (NK) cells
- innate lymphoid cells (ILCs)

- receptors that recognize molecules from infectious organisms - PAMPS
- part of the internal defense system

- pathogen-associated molecular patterns (PAMPs) that are molecules from pathogens
- when bound to a pathogen, they activate phagocytic cells

on the surface of macrophages, dendritic cells, neutrophils, eosinophils, monocytes, mast cells, T cells, and epithelial cells

Toll-like receptors (TLRs)
C-type lectin receptors (CLRs)
RIG-1-like receptors (RLRs)
NOD-like receptors (NLRs)

- PRRs that are toll-like receptors
- glycoproteins that bind to microbial substances, activating cytokine and chemokine production and other processes
- phagocytosis is enhanced and adaptive immunity is triggered, destroyiing pathogens before disease sets in

- 10 types
- some on cell surfaces (1, 2, 4, 5, 6)
- some in the cytoplasm (3, 7, 9)

type of PRR that are soluble factors normally found in serum
part of the internal defense system

- increase rapidly in response to infection, injury, trauma
- facilitate contact btwn microbes and phagocytic cells
- limit host tissue destruction caused by proteolytic enzyme release during phagocytosis
- bind to, and recyle important proteins and minerals during inflammation

1. C-reactive protein (CRP)
2. Fibrinogen
3. Haptoglobin
4. Complement C3

- opsonization
- complement activation

clot formation

- opsonization
- lysis

- part of the internal defense system
- the body's overall rxn to injury or invasion by an infectious agent
- there are 4 cardinal signs and symptoms

- redness (erythema)
- swelling (edema)
- heat
- pain

selectin and integrins are ADHESION molecules required for binding of phagocyte to endothelial cells on the vessel wall

chemotaxis is the directional movement of phagocytes towared the pathogen (infection site) along a density gradient

Chemotactic factors attract phagocytes to inflammation/infection site, such as LPS (lipopolysacharide), cytokines such as IL-8

- phagocytic cells attracted to site of inflammation
- process is enhanced by opsonins like CRP

- a substance that covers (coats) the pathogen which is phagocytized faster and more effectively
- process is called opsonization

- C reactive protein (CRP)
- antibody (immunoglobulin)
- C3b molecules

- oxidative burst
- O2 independent pathway

HMP shunt converts NADP to NADPH
O2 is converted to O2-
then O2- to H2O2 and OH-

The pH of the cell is altered, leading to activation of lytic enzymes such as defensins

- part of the internal defense system
- they are the first line of defense against cells that are virally infected, cells infected iwht other intracellular pathogens, and tumor cells
- they recognize altered structures on damaged cells and can eliminate them without prior exposure

- it is enhanced by certain cytokines (IL-2, IFM-alpha, IFN-beta), which rise rapidly during viral infections
- they produce other cytokines that recruit T cells and aid in development of granulocytes and macrophages

- Inhibition
- Activation
- Antibody-coated target cell

- specific to each pathogen or microbial agent
- remembers prior exposure due to clonal selection, expansion and differentiation of antigen-specific T and B cells
- increases response to a pathogen upon repeated exposure
- initially, takes longer to become activated but is longer lasting
- involves T and B lymphocytes

- tailored response
- specificity for earch pathogen
- memory
- increased and faster secondary response
- takes time with the first exposure