Immune System

Primary organs vs. Secondary organs

Primary organs are where immune cells are made and mature (Red Bone Marrow, Thymus), whereas Secondary organs are where immune cells circulate

Leukocytes - VISUAL

-PHILS are…

granulocytes

A macrophage is a monocyte that…

has left blood

5 factors/actions of the 2nd line defense (innate immunity)

1. Phagocytes

2. NK cells

3. Inflammation

4. Antimicrobial proteins (complement)

5. Fever

Adaptive immunity - Humoral

B cells

• Plasma cells

• Memory B

Adaptive immunity - Cell-mediated

CD4

• Helper T cells (T_H)

• Regulatory T cells (T_R)

• Memory T_H

CD8

• Cytotoxic T cells (T_C)

• Memory T_C

1st line - Skin surface barriers (5)

• Hair: trap

• Keratin: protein layer makes it difficult for pathogens to pass

• Sweat, dermcidin: acidic, dermcidin —> increases ion absorption by pathogens —> causes them to lyse

• Sebum: acidic

• Defensins: increases water absorption into pathogens —> lyse

1st line - Mucus membrane barriers (5)

Chemical and physical features

• Mucus —> thick substance prevent penetration by pathogens

• Hairs —> trap

• Cilia —> trap and move away

• Acidic environment —> e.g. stomach, vagina

• Lysozymes —> breakdown pathogens

2nd line - Phagocytes

• Neutrophils, Monocytes (blood) & Macrophages (tissues)

• Phagocytosis - vesicle fuses with lysosomes - lysosome digestive enzymes breakdown pathogens

2nd line - NK cells

• Derived from lymphocytes

• Detect abnormal cells

• Release:

1. Perforins - makes hole in pathogen

2. Granzymes - enter pathogen and digest them

Inflammation (4 benefits, 5 signs, 3 processes)

Benefits: (4)

• Flood with WBCs

• Alert adaptive

• Clean debris

• Healing

Signs:

• Heat

• Redness

• Swelling

• Pain

• Immobilization

Process:

1. Chemical release of histamine (baso, mast, prostaglandins, kinins)

2. Vasodilation (redness, heat) - increase blood flow

3. Phagocyte mobilization - chemical adhesion molecules (CAMS) on endothelium of capillary will stop neutrophils IN THEIR TRACKS TO RECUTE THEM - to enter tissue injury site

Antimicrobial proteins (complement)

• Interferons - stop viral replication

• Complement proteins

Complement System (+3 functions)

• 20 plasma proteins

• Activated by antibodies, lectins, spontaneously

Functions:

1. Enhance inflammation

2. Opsonization - tag antigens to stimulate phagocytosis

3. Make MAC (membrane attack complex) proteins enter pathogen and allows water to go in —> lyse

Fever (benefits & negative impact)

• Monocytes, lymphocytes

• Pyrogens released by leukocytes

Benefits of low-grade fever:

• Zinc retention limits bacterial growth

• Increased body temp. can increase metabolic rate

Negative impact:

• High fever denatures proteins

Naive B cell immunocompetence

Have the ability to recognize a specific antigen and display a specific antigen receptor (membrane bound antibodies) on its plasma membranes

• Recognize free antigen

• Display receptors IgM or IgD

Naive B cell activation

1. Binds to an antigen

2. Cross linked formed (2 antigen binding sites are bound)

3. B cell activated to divide

• Without Helper T, response is much slower

4. Divides into: few memory B cells, many plasma cells that will produce antibodies

Antibodies are also called… and are produced by…

immunoglobulins… plasma cells

Antigens

• They are generally proteins

• How are they recognized? By shape

• Complete antigens:

- Reactive: with immune cells (lymphocytes) or antibodies

- Immunogenic: stimulate immune cells (lymphocytes) to divide

IgM

• Monomer or pentamer (5x = makes it a potent agglutination agent, in blood, lymph)

• 1st to site (indicates current infection)

• Also acts as a B cell receptor

IgA

• Monomer or dimer (2x)

• Secretions (sweat, milk, saliva, intestinal juice)

• Helps stop pathogens from attaching to epithelial cell surface

IgD

• Monomer

• As a B cell receptor

IgG

• Monomer (blood, lymph)

• Most abundant secondary exposure

• Cross placenta

IgE

• Monomer (blood)

• Allergic response

Antibody Mechanisms - PLAN

Precipitation: Clump antigens to promote phagocytosis (small pieces)

Lyse via Complement: by MAC —> activate complement to make MAC

Agglutination: clump to promote phagocytosis (cells)

Neutralization: block pathogen from releasing toxins or entering cells

Humoral Immunity - Active vs Passive

Memory B Cells

Naive B cells divide into Plasma cells (antibodies) + Memory B cells (fewer, but circulate potentially lifetime)

1st exposure plasma 5-7 days to make antibodies

Future exposure 1-2 days and much more antibodies produced by memory cells

Cell-medicated immunity — T_H, T_R, T_C

T_H - activates B cells, T_C, phagocytes

T_R - dampen immune response (prevent autoimmune response)

T_C - release perforins and granzymes to lyse infected cells

2 steps for immunocompetence:

1. Positive selection

T cell receptor must bind perfectly with major histocompatibility complete (MHC) (protein on cell membrane) on antigen presenting cell (APC). If yes, moves on to step 2. If no, apoptosis

2. Negative selection

T cell receptor must not bind perfectly (too strongly) to self-antigen on the MHC. If yes, it can leave and circulate the body. If it does bind —> apoptosis

(if it binds too strongly, risk of autoimmune - our cells attack our body)

Naive T cell Activation

Requires: Helper T

Examples of APCs: Dendritic, Macrophages, B cell

MHC2: APC

MHC1: Infected cell

1. Pathogen ingested by APC and foreign antigens are presented on MHC2 of APC

2. T cell receptor (TCR) on T_H binds to MHC 2 on APC and CD4 acts as a co-receptor (in case, failsafe) and also binds

3. This stimulates T_H to release cytokines (proteins, different types, to stimulate immune activity)

4. Cytokines stimulate T_C to proliferate/divide and look for infected cells

5. T cell receptor on T_C binds to MHC 1 on an infected cell and CD8 also binds

6. T_C release perforins (poke a hole in infected cell) and granzymes (digest infected cell) to kill infected cell

Self-antigens

• Self-antigens are bound to all cells

• MHC1: on nucleated cell

• MHC2: APC

APCs (3)

Macrophages, Dendritic cells, B cells